• A GPT Database of Exosome Functionality •

Exosome Research Publication Analysis

DATE OF PUBLICATION 1987

TITLE OF DOCUMENT Vesicle Formation during Reticulocyte Maturation

Subtitle: ASSOCIATION OF PLASMA MEMBRANE ACTIVITIESWITH RELEASED VESICLES (EXOSOMES)*

AUTHORS Rose M. Johnstone, Mohammed Adam, James R. Hammond, Linda Orr, Claire Turbide

OVERVIEW The document presents an analysis of vesicle formation during the in vitro maturation of sheep reticulocytes. It explores how these vesicles, which contain various activities characteristic of the reticulocyte plasma membrane, are released as reticulocytes mature into erythrocytes. The vesicles' composition and activities reflect the changing nature of the plasma membrane during reticulocyte maturation, and the study suggests that vesicle externalization is a mechanism for shedding specific membrane functions as reticulocytes transition to erythrocytes.

RESULTS The study observed that vesicles formed from cultured reticulocytes contained a limited number of peptides, particularly a 94 kDa peptide identified as the transferrin receptor and a 70-72 kDa peptide identified as clathrin-uncoating ATPase. The vesicles were not merely fragments of plasma membrane and were distinct in composition from mature red cell cultures. They contained activities like acetylcholinesterase, cytochalasin B binding (glucose transporter), nucleoside binding (nucleoside transporter), Na+-independent amino acid transport, and the transferrin receptor. Moreover, the lipid composition of these vesicles reflected high sphingomyelin content, characteristic of sheep red cell plasma membranes.

CELL TYPE(S)

• Sheep Reticulocytes

DISEASES ADDRESSED Not Applicable

EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS

• Transferrin Receptor

• Clathrin-uncoating ATPase

EXOSOME CARGOS

Cytokines Not mentioned

Enzymes

• Acetylcholinesterase​​

• Glyceraldehyde-3-phosphate dehydrogenase​​

Growth Factors Not mentioned

Nucleic Acids (RNA or DNA) Not mentioned

Proteins

• Transferrin Receptor (94 kDa)​​

• Clathrin-uncoating ATPase (70-72 kDa)​​

Transcription Factors (O,S,K,M, Nanog) Not mentioned

REFERENCES

• The study was supported by the Alberta Heritage Foundation for Medical Research and the Fonds de la Recherche en Santé du Québec​​.

This document does not contain detailed references to other manuscripts that focus on the subject matter of any of the headers or specifically on exosomes.

 **DATE OF PUBLICATION**

- **Published online January 16, 2015**

**TITLE OF DOCUMENT**

- **Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury**

**AUTHORS**

- **Yanlu Zhang MD, Michael Chopp PhD, Yuling Meng PhD, Mark Katakowski PhD, Hongqi Xin PhD, Asim Mahmood MD, and Ye Xiong MD PhD**

**OVERVIEW**

- The study investigated the effect of exosomes derived from multipotent mesenchymal stromal cells (MSCs) on functional recovery and neurovascular remodeling in rats after traumatic brain injury (TBI). The hypothesis was that systemic administration of cell-free exosomes generated from MSCs could promote functional recovery and neurovascular remodeling post-TBI.

**RESULTS**

- Exosome-treated rats showed significant improvement in spatial learning and sensorimotor functional recovery. Notably, there was an increase in the number of newly generated endothelial cells and newly formed immature and mature neurons in the dentate gyrus, alongside a reduction in neuroinflammation.

**CELL TYPE(S)**

- Mesenchymal stromal cells (MSCs)

**DISEASES ADDRESSED**

- Traumatic brain injury (TBI)

**ENVELOPE PROTEINS and SURFACE RECEPTORS**

- Not Applicable

**EXOSOME CARGOS**

- **Proteins:** Exosomes contained proteins.

- **mRNAs and microRNAs (miRNAs):** Exosomes also contained mRNAs and microRNAs【15†source】.

**REFERENCES**

- The references section is acknowledged but not detailed here【17†source】.

 **DATE OF PUBLICATION**

2016

**TITLE OF DOCUMENT**

Comparative Analysis of Human Mesenchymal Stem Cells Derived From Bone Marrow, Placenta, and Adipose Tissue as Sources of Cell Therapy

**AUTHORS**

Young-Joo Jeon, Jumi Kim, Jin Hyoung Cho, Hyung-Min Chung, Jung-Il Chae

**OVERVIEW**

This study investigates mesenchymal stem cells (MSCs) derived from human bone marrow (BM), placenta (PL), and adipose tissue (AT). It focuses on their phenotype, surface antigen expression, differentiation ability, proteome reference map, and therapeutic efficacy in a hindlimb ischemic disease model. The research reveals that despite similar phenotypic and cytological characteristics, MSCs from these different sources exhibit varying differentiation potentials and express around 90 differentially regulated proteins, mainly involved in cytoskeletal functions, oxidative stress, peroxiredoxin, and apoptosis. Particularly, PL-MSCs demonstrated higher therapeutic efficacy in the hindlimb ischemic disease model, suggesting that these cells have certain biological advantages for clinical applications in cell therapy【10†source】【11†source】.

**RESULTS**

The key results include:

1. Differentiation potentials of MSCs vary depending on their source (BM, PL, AT).

2. Identification of approximately 90 differentially regulated proteins, with roles in cytoskeletal function, oxidative stress, peroxiredoxin, and apoptosis.

3. Higher therapeutic efficacy of PL-MSCs in a hindlimb ischemic disease model compared to BM- and AT-MSCs【11†source】.

**CELL TYPE(S)**

- Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs)

- Placenta-derived Mesenchymal Stem Cells (PL-MSCs)

- Adipose Tissue-derived Mesenchymal Stem Cells (AT-MSCs)【12†source】

**DISEASES ADDRESSED**

- Hindlimb ischemic disease【13†source】

**ENVELOPE PROTEINS and SURFACE RECEPTORS**

Not Applicable

**EXOSOME CARGOS**

Not Applicable

**PROTEINS**

The study identified numerous proteins, including but not limited to:

- Vimentin

- Tropomyosin (b chain, a-1 chain)

- Protein NDRG1

- Mannose-6-phosphate receptor-binding protein 1

- Phosphoglycerate kinase 1

- Calponin-2

- Annexin A4

- Superoxide dismutase [Cu-Zn]

- Heat shock proteins (b-1, b-6)

- Stathmin

- Transgelin-2

- Cytochrome b5

- L-lactate dehydrogenase B chain

- Nucleoside diphosphate kinase B

For a complete list, refer to Table I in the document【14†source】.

**REFERENCES**

Journal of Cellular Biochemistry 117:1112–1125 (2016)【15†source】.

 **DATE OF PUBLICATION**

- **Published: Unknown (Accepted: 29 March 2017)**

**TITLE OF DOCUMENT**

- **Age-Related Changes in Plasma Extracellular Vesicle Characteristics and Internalization by Leukocytes**

**AUTHORS**

- **Erez Eitan, Jamal Green, Monica Bodogai, Nicolle A. Mode, Rikke Bæk, Malene M. Jørgensen, David W. Freeman, Kenneth W. Witwer, Alan B. Zonderman, Arya Biragyn, Mark P. Mattson, Nicole Noren Hooten, & Michele K. Evans**

**OVERVIEW**

- This study analyzed circulating plasma extracellular vesicles (EVs) in a cross-sectional and longitudinal manner to understand age-related changes in EV characteristics and their internalization by leukocytes. It was found that EV concentration decreases with advancing age and that EVs from older individuals are more readily internalized by B cells and increase MHC-II expression on monocytes, compared with EVs from younger individuals.

**RESULTS**

- The study reported a significant decrease in EV concentration with age, without notable changes in EV size. It also found increased internalization of aged EVs by B cells and a resultant effect on monocyte activation, without a significant change in B cell activation.

**CELL TYPE(S)**

- B cells, Monocytes

**DISEASES ADDRESSED**

- Age-related diseases (e.g., cancer, neurodegenerative, metabolic, and cardiovascular diseases)

**ENVELOPE PROTEINS and SURFACE RECEPTORS**

- Not Applicable

**EXOSOME CARGOS**

- **Proteins:** Notable changes in protein levels with age were observed, including significant decreases in several apoptosis markers (p53, cleaved PARP, cleaved Caspase-3) and increases in proteins like CD151 and MUCIN16.

- **RNA:** Not specifically mentioned, but EVs generally contain RNA.

**REFERENCES**

- Not detailed in the provided quotes.

 **DATE OF PUBLICATION**

- **Published: December 19, 2017**

**TITLE OF DOCUMENT**

- **Extracellular vesicles and aging**

**AUTHORS**

- **Paul D. Robbins**

**OVERVIEW**

- The article discusses the impact of aging and related chronic diseases on healthcare systems, emphasizing the need to understand the mechanisms of aging. It highlights the role of cell autonomous and non-autonomous mechanisms in aging, including the contribution of senescent cells and their secretory phenotype (SASP). It focuses on the diverse roles of extracellular vesicles (EVs) in modulating immune responses, angiogenesis, and tissue regeneration, and how they might influence aging processes through cell non-autonomous mechanisms. Senescent cells release more EVs with different compositions, which could contribute to the adverse effects of senescence on aging. The article also explores the potential of EVs from progenitor cells for therapeutic applications to extend healthspan and as biomarkers for unhealthy aging.

**RESULTS**

- The article outlines the complexities of the aging process, involving genetic and environmental factors, and the accumulation of molecular and cellular damage. It discusses the role of senescent cells in aging and the potential impact of their EVs on aging-related pathologies. It also highlights the loss of regenerative capacity in aging, particularly in stem cells, and the therapeutic potential of stem cell-derived EVs in extending healthspan and lifespan.

**CELL TYPE(S)**

- Senescent cells, Mesenchymal stem cells (MSCs), Progenitor cells

**DISEASES ADDRESSED**

- Aging-related diseases, Chronic diseases

**ENVELOPE PROTEINS and SURFACE RECEPTORS**

- Not Applicable

**EXOSOME CARGOS**

- **Proteins, Lipids, mRNAs, and non-coding RNAs (ncRNAs) including miRNAs:** These cargos are derived from the parental cells and are present in EVs, including both exosomes and microvesicles.

**REFERENCES**

- The references section is acknowledged but not detailed here【46†source】.

 DATE OF PUBLICATION

• Published online 26 July 2017​​.

TITLE OF DOCUMENT

• Hypothalamic stem cells control ageing speed partly through exosomal miRNAs​​.

AUTHORS

• Yalin Zhang, Min Soo Kim, Baosen Jia, Jingqi Yan, Juan Pablo Zuniga-Hertz, Cheng Han, & Dongsheng Cai​​.

OVERVIEW

• This research explores the influence of hypothalamic stem/progenitor cells on the ageing process in mice, highlighting the role of these cells in modulating ageing speed. The study particularly focuses on how the decline or augmentation of these cells in the hypothalamus impacts lifespan and physiological changes associated with ageing. The key mechanism proposed involves the secretion of exosomal miRNAs by these stem cells​​.

RESULTS

• Key findings include the observation that loss of hypothalamic stem/progenitor cells leads to accelerated ageing, while their restoration can slow down ageing. Experiments demonstrated that these cells, especially when modified to resist inflammatory environments, could extend lifespan and counteract ageing-related physiological declines. The role of exosomal miRNAs secreted by these cells was emphasized in the regulation of ageing​​.

CELL TYPE(S)

• Hypothalamic stem/progenitor cells (htNSCs)

• Neurons (MBH neuronal subtypes POMC and AgRP neurons)​​.

DISEASES ADDRESSED

• Ageing and ageing-related physiological declines​​.

ENVELOPE PROTEINS and SURFACE RECEPTORS

• Not Applicable (No specific information provided in the analyzed sections).

EXOSOME CARGOS

• Cytokines

  • Not Applicable (No specific information provided in the analyzed sections).

• Enzymes

  • Not Applicable (No specific information provided in the analyzed sections).

• Growth Factors

  • Not Applicable (No specific information provided in the analyzed sections).

• Nucleic Acids (RNA or DNA)

  • Exosomal miRNAs (Specific inventor of miRNA’s in the figure below)​​.

• Proteins

  • Not Applicable (No specific information provided in the analyzed sections).

• Transcription Factors (OSKM, Nanog)

  • Not Applicable (No specific information provided in the analyzed sections).

REFERENCES

• Not Applicable (No additional references relevant to the Subject Headers are listed in the provided sections).

 **DATE OF PUBLICATION**

- June 3, 2017【9†source】.

**TITLE OF DOCUMENT**

- Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use【10†source】.

**AUTHORS**

- Mario Gimona, Karin Pachler, Sandra Laner-Plamberger, Katharina Schallmoser, Eva Rohde【10†source】.

**OVERVIEW**

- The document discusses the therapeutic potential of extracellular vesicles (EVs) derived from stem and progenitor cells, focusing on their development for clinical use. It highlights the significance of understanding the source cell types, target diseases, and the regulatory requirements for manufacturing and testing EV-based therapies. Emphasis is given to mesenchymal stromal cell (MSC)-derived EV therapies for diseases such as critical size bone defects, epidermolysis bullosa, and spinal cord injury. The identification of the mode of action (MoA) of EV-based therapies remains a major challenge in translating these therapies from the lab to clinical application【11†source】.

**RESULTS**

- This section outlines the advancement of MSC-EV-based therapies, detailing preclinical testing and the hurdles faced in the development of cell or EV-based therapeutics. It emphasizes the importance of defining early manufacturing steps, characterization procedures, and potency assays for EV-based therapeutics. The discussion includes critical size bone defects, epidermolysis bullosa (EB), and spinal cord injury (SCI) as specific target diseases for these therapies【12†source】【13†source】【14†source】【15†source】.

**CELL TYPE(S)**

- Mesenchymal Stromal Cells (MSCs).

**DISEASES ADDRESSED**

- Critical size bone defects

- Epidermolysis bullosa (EB)

- Spinal cord injury (SCI)

**EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS**

- Not explicitly mentioned.

**EXOSOME CARGOS**

- **Cytokines**: Not explicitly mentioned.

- **Enzymes**: Not explicitly mentioned.

- **Growth Factors**: Not explicitly mentioned.

- **Nucleic Acids (RNA or DNA)**: Mention of microRNA (miRNA)-133 in the context of SCI repair【15†source】.

- **Proteins**: Not explicitly mentioned.

- **Transcription Factors (OSKM, Nanog)**: Not explicitly mentioned.

**REFERENCES**

- The document includes references related to the development, characterization, and therapeutic applications of EVs and EV-based therapies. Some key references include studies on membrane vesicles and extracellular vesicles, dendritic cell-derived exosomes, clinical grade exosomes, and EVs in clinical trials【18†source】.

 **DATE OF PUBLICATION**

- 2018

**TITLE OF DOCUMENT**

- Exosomes Derived from Human Induced Pluripotent Stem Cells Ameliorate the Aging of Skin Fibroblasts

**AUTHORS**

- Myeongsik Oh, Jinhee Lee, Yu Jin Kim, Won Jong Rhee, Ju Hyun Park

**OVERVIEW**

- This study investigates the effect of exosomes derived from human induced pluripotent stem cells (iPSC-Exo) on aging human dermal fibroblasts (HDFs). The research primarily focuses on the ameliorative effects of iPSC-Exo on skin fibroblasts, particularly against aging and UVB-induced damage, by examining cell proliferation, migration, and changes in gene expression.

**RESULTS**

- iPSC-Exo stimulated the proliferation and migration of HDFs. It protected HDFs from UVB-induced damage, inhibited overexpression of matrix-degrading enzymes, and increased collagen type I expression in photo-aged HDFs. iPSC-Exo also reduced senescence-associated β-galactosidase (SA-β-Gal) expression, MMP-1/3 levels, and restored collagen type I expression in senescent HDFs.

**NOTES**

In the study "Exosomes from Adipose-Derived Stem Cells Overexpressing Nrf2 Accelerate Cutaneous Wound Healing by Promoting Vascularization in a Diabetic Foot Ulcer Rat Model," the adipose-derived stem cells (ADSCs) were genetically modified to overexpress Nrf2. This overexpression was not a natural expression but an induced one. The researchers isolated exosomes from both the Nrf2-overexpressing ADSCs and the wild-type ADSCs. It was observed that the expression of Nrf2 in exosomes from the Nrf2-overexpressing ADSCs was increased compared to that in exosomes from wild-type ADSCs​​. This indicates that the Nrf2 overexpression was a result of the genetic modification of the ADSCs, and the exosomes derived from these modified cells carried the overexpressed Nrf2.

**CELL TYPE(S)**

- Human Induced Pluripotent Stem Cells (iPSCs)

- Human Dermal Fibroblasts (HDFs)

**DISEASES ADDRESSED**

- Skin Aging

- Photoaging

**EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS**

- Not specifically mentioned

**EXOSOME CARGOS**

- The specific contents of the iPSC-Exo were not detailed in the analyzed sections of the document.

> Cytokines

> Enzymes

> Growth Factors

> Nucleic Acids (RNA or DNA)

> Proteins

> Transcription Factors (OSKM, Nanog)

**REFERENCES**

- The references section was not analyzed in detail, but it likely contains studies related to skin aging, iPSCs, exosomes, and their therapeutic applications. Specific references can be provided upon request.

Please let me know if you need more detailed information on any of these sections, including a deeper analysis of the references.

 **DATE OF PUBLICATION**

- 2018

**TITLE OF DOCUMENT**

- Exosomes from Adipose-Derived Stem Cells Overexpressing Nrf2 Accelerate Cutaneous Wound Healing by Promoting Vascularization in a Diabetic Foot Ulcer Rat Model

**AUTHORS**

- Xue Li, Xiaoyun Xie, Weishuai Lian, Rongfeng Shi, Shilong Han, Haijun Zhang, Ligong Lu, Maoquan Li

**OVERVIEW**

- This study explores the role of exosomes derived from adipose-derived stem cells (ADSCs) overexpressing Nrf2 in accelerating wound healing, particularly in a diabetic foot ulcer rat model. It examines the effect of these exosomes on endothelial progenitor cells (EPCs) under high glucose conditions and their impact on angiogenesis, oxidative stress, and inflammation.

**RESULTS**

- The study found that exosomes from ADSCs, especially those overexpressing Nrf2, reduced apoptosis, oxidative stress, and inflammation in EPCs under high glucose conditions. They enhanced tube formation, cell viability, and angiogenesis, indicating a potential for improved wound healing in diabetic foot ulcers. Additionally, these exosomes increased the levels of SMP30, VEGF, and phosphorylated VEGFR2, while decreasing NOX1 and NOX4 levels.

**CELL TYPE(S)**

- Adipose-Derived Stem Cells (ADSCs)

- Endothelial Progenitor Cells (EPCs)

**DISEASES ADDRESSED**

- Diabetic Foot Ulcers (DFU)

**EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS**

- CD4

- CD63

- TSG101

**EXOSOME CARGOS**

- Not specified in detail, but involves various proteins that influence angiogenesis and oxidative stress.

> Cytokines

> Enzymes

> Growth Factors

> Nucleic Acids (RNA or DNA)

> Proteins

> Transcription Factors (OSKM, Nanog)

**REFERENCES**

- The references section requires detailed analysis to extract specific references related to the subject headers. If needed, I can provide a comprehensive list of these references.

Please let me know if you need further detailed information or analysis of specific sections, including a detailed examination of the references.

 **DATE OF PUBLICATION**

- May 23, 2018

**TITLE OF DOCUMENT**

- Exosomes secreted by placental stem cells selectively inhibit growth of aggressive prostate cancer cells

**AUTHORS**

- Taylor C. Peak, Prakash Praharaj, Gati K. Panigrahi, Michael Doyle, Yixin Su, Isabel R. Schlaepfer, Ravi Singh, Donald J. Vander Griend, Julie Alickson, Ashok Hemal, Anthony Atala, Gagan Deep

**OVERVIEW**

- This study explores the characterization of placental-derived stem cell (PLSC) exosomes (PLSCExo) and their anti-cancer efficacy in prostate cancer (PCa) cell lines. The research focuses on the selective inhibition of aggressive prostate cancer cell growth by these exosomes, emphasizing the need for targeted therapies in cancer treatment. The PLSCExo exhibited strong inhibitory effects on the viability of both sensitive and resistant PCa cell lines, while showing no significant effect on non-neoplastic human prostate cell lines.

**RESULTS**

- The study demonstrated that PLSCExo treatment significantly inhibited the viability of various prostate cancer cell lines, both enzalutamide-sensitive and -resistant. This inhibition ranged from 30% to 44% compared to controls. Interestingly, PLSCExo had no significant effect on the viability of non-neoplastic prostate cells. The research also highlighted the role of retinoic acid receptor/liver x receptor pathways in the biological effects of PLSCExo.

**CELL TYPE(S)**

- Prostate Cancer Cell Lines (C4-2B, CWR-R1, LNCaP)

- Non-neoplastic Human Prostate Cell Line (PREC)

**DISEASES ADDRESSED**

- Prostate Cancer

**EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS**

- Not specifically mentioned in the document.

**EXOSOME CARGOS**

- **Cytokines**

- Not specifically mentioned in the document.

- **Enzymes**

- Not specifically mentioned in the document.

- **Growth Factors**

- Not specifically mentioned in the document.

- **Nucleic Acids (RNA or DNA)**

- Not specifically mentioned in the document.

- **Proteins**

- 241 proteins loaded in PLSCExo (specific proteins not listed).

- **Transcription Factors (OSKM, Nanog)**

- Not specifically mentioned in the document.

**REFERENCES**

- The references section contains numerous studies, but without specific reference numbers in the text, it's challenging to link them directly to the subject headers. Further analysis is required to determine if any references are directly relevant to the headers.

This document presents a comprehensive overview of the use of placental stem cell-derived exosomes in targeting prostate cancer cells, indicating a promising area of research in cancer treatment.

 **DATE OF PUBLICATION**

- May 23, 2018

**TITLE OF DOCUMENT**

- Exosomes secreted by placental stem cells selectively inhibit growth of aggressive prostate cancer cells

**AUTHORS**

- Taylor C. Peak, Prakash Praharaj, Gati K. Panigrahi, Michael Doyle, Yixin Su, Isabel R. Schlaepfer, Ravi Singh, Donald J. Vander Griend, Julie Alickson, Ashok Hemal, Anthony Atala, Gagan Deep

**OVERVIEW**

- This study explores the characterization of placental-derived stem cell (PLSC) exosomes (PLSCExo) and their anti-cancer efficacy in prostate cancer (PCa) cell lines. The research focuses on the selective inhibition of aggressive prostate cancer cell growth by these exosomes, emphasizing the need for targeted therapies in cancer treatment. The PLSCExo exhibited strong inhibitory effects on the viability of both sensitive and resistant PCa cell lines, while showing no significant effect on non-neoplastic human prostate cell lines.

**RESULTS**

- The study demonstrated that PLSCExo treatment significantly inhibited the viability of various prostate cancer cell lines, both enzalutamide-sensitive and -resistant. This inhibition ranged from 30% to 44% compared to controls. Interestingly, PLSCExo had no significant effect on the viability of non-neoplastic prostate cells. The research also highlighted the role of retinoic acid receptor/liver x receptor pathways in the biological effects of PLSCExo.

**CELL TYPE(S)**

- Prostate Cancer Cell Lines (C4-2B, CWR-R1, LNCaP)

- Non-neoplastic Human Prostate Cell Line (PREC)

**DISEASES ADDRESSED**

- Prostate Cancer

**EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS**

- Not specifically mentioned in the document.

**EXOSOME CARGOS**

- **Cytokines**

- Not specifically mentioned in the document.

- **Enzymes**

- Not specifically mentioned in the document.

- **Growth Factors**

- Not specifically mentioned in the document.

- **Nucleic Acids (RNA or DNA)**

- Not specifically mentioned in the document.

- **Proteins**

- 241 proteins loaded in PLSCExo (specific proteins not listed).

- **Transcription Factors (OSKM, Nanog)**

- Not specifically mentioned in the document.

**REFERENCES**

 
DATE OF PUBLICATION

• 2018

TITLE OF DOCUMENT

• Possibility of Exosome-Based Therapeutics and Challenges in Production of Exosomes Eligible for Therapeutic Application

AUTHORS

• Takuma Yamashita, Yuki Takahashi, Yoshinobu Takakura

OVERVIEW

• This review discusses the therapeutic potential of exosomes and the challenges in their production for therapeutic applications. Exosomes, cell-derived vesicles, have been recognized for their capacity to deliver biological molecules, which could be harnessed for therapeutic purposes. However, there are significant hurdles, such as their heterogeneity, low productivity, and the need for optimized production methods, including isolation and storage. The review also explores the improvement of therapeutic potential and delivery efficiency of exosomes.

RESULTS

• The review summarizes the current understanding of the therapeutic application of exosomes, including their role in regenerative and anti-inflammatory therapies, and as cancer vaccines. It highlights the challenges in large-scale production and the collection of high-quality, uniform exosomes. Various strategies for enhancing the therapeutic potential of exosomes, such as overexpression of therapeutic molecules and modifications, are discussed. The review also covers aspects of exosome delivery, including biodistribution and the role of macrophages in their clearance.

CELL TYPE(S)

• Mesenchymal stem cells (MSCs)

• Dendritic cells

• Cancer cells

• Induced pluripotent stem cell (iPS cell)-derived MSC

• Cardiomyocyte progenitor cells

DISEASES ADDRESSED

• Cancer

• Cardiovascular diseases

• Diabetes

• Alzheimer’s disease

• Organ injury (liver, renal, neural)

• Osteoarthritis

• Acute kidney injury

EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS

• CD9

• CD63

• Alix

• Major histocompatibility complex (MHC)-I

• MHC-II

• Co-stimulating factor CD86

• NKG2D ligand

• IL-15Rα

EXOSOME CARGOS

Cytokines

• Interleukin-10 (IL-10)

Enzymes

• Not specifically mentioned

Growth Factors

• Transforming growth factor-β (TGF-β)

Nucleic Acids (RNA or DNA)

• mRNA

• microRNAs (miRNAs)

Proteins

• Not specifically mentioned

Transcription Factors (OSKM, Nanog)

• Not specifically mentioned

REFERENCES

• References relevant to the topics in the review:

  1. Théry, C., Ostrowski, M., & Segura, E. (2009). Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol., 9, 581–593.

  2. Baietti, M. F., Zhang, Z., Mortier, E., Melchior, A., Degeest, G., Geeraerts, A., ... & David, G. (2012). Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol., 14, 677–685.

  3. Trajkovic, K., Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., ... & Simons, M. (2008). Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 319, 1244–1247.

  4. Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol., 9, 654–659.

  5. Andre, F., Chaput, N., Schartz, N. E., Flament, C., Aubert, N., Bernard, J., ... & Zitvogel, L. (2004). Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J. Immunol., 172, 2126–2136.

(Note: The list of references is not exhaustive and includes only selected references directly relevant to the topics in the document.)

◉ Exosome Research Publication Analysis. (AGING)

DATE OF PUBLICATION

• The document was received on November 19, 2018, accepted for publication on February 17, 2019, and first published online on February 27, 2019​​.

TITLE OF DOCUMENT

• Highly Purified Human Extracellular Vesicles Produced by Stem Cells Alleviate Aging Cellular Phenotypes of Senescent Human Cells​​.

AUTHORS

• Senquan Liu, Vasiliki Mahairaki, Hao Bai, Zheng Ding, Jiaxin Li, Kenneth W. Witwer, Linzhao Cheng​​.

OVERVIEW

• This study examines the properties and functions of extracellular vesicles (EVs), including exosomes and microvesicles, from human induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs). It highlights that iPSCs produce significantly more EVs than MSCs. These EVs, particularly from iPSCs, are shown to reduce reactive oxygen species levels and alleviate aging phenotypes in senescent MSCs, suggesting their potential in treating aging and degenerative diseases​​.

RESULTS

• The research demonstrated that highly purified iPSC-derived EVs efficiently enter target cells and reduce cellular reactive oxygen species (ROS), thus alleviating aging phenotypes of senescent MSCs. The study showed that iPSC-EVs were more effective in this role compared to MSC-EVs, producing a more significant increase in cell growth and reduction of aging markers in treated senescent cells​​.

CELL TYPE(S)

• Human induced pluripotent stem cells (iPSCs)

  • BC1 iPSC Line: This line was reprogrammed from the blood cells of a healthy male donor.

  • WT4 iPSC Line: This line was reprogrammed from the fibroblasts of a healthy female donor.

• Mesenchymal stem cells (MSCs)​​

• These iPSC lines were derived from diverse types of somatic cells of both genders. Additionally, the study also used four different mesenchymal stem cell (MSC) preparations derived from three genetically distinct donors​​.

These iPSC lines were derived from diverse types of somatic cells of both genders. Additionally, the study also used four different mesenchymal stem cell (MSC) preparations derived from three genetically distinct donors​​.

DISEASES ADDRESSED

• Not Applicable

EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS

• CD81

• TSG101

• Syntenin​​

EXOSOME CARGOS

• Cytokines: Not explicitly listed in the document.

• Enzymes: Peroxiredoxin (PRDX) family members, including PRDX1 and PRDX2​​.

• Growth Factors: Not explicitly listed in the document.

• Nucleic Acids (RNA or DNA): Not explicitly listed in the document.

• Proteins: CD9, CD63, CD81, PRDX1, PRDX2​​.

• Transcription Factors (OSKM, Nanog): Not explicitly listed in the document.

Exosome Research Publication Analysis

DATE OF PUBLICATION

• 2019

TITLE OF DOCUMENT

• The Role of Exosomes in Regenerative Medicine

AUTHORS

• Douglas Spiel MD

OVERVIEW

• The document is an extensive exploration of the role of extracellular vesicles, particularly exosomes and microvesicles, in regenerative medicine. It discusses the characteristics of these vesicles, their therapeutic benefits, including immunomodulatory and trophic effects, and their potential in treating a variety of diseases.

RESULTS

• Key findings include the detailed understanding of mesenchymal stem cell-derived exosomes (MSC EVs) and their therapeutic implications in various medical conditions. It covers how MSC EVs can affect cellular processes and contribute to disease treatment, particularly through their anti-inflammatory, anti-fibrotic, and anti-apoptotic effects.

CELL TYPE(S)

• Mesenchymal stem cells (MSCs)

• Tissue-resident stem cells

• Chondrocyte progenitor cells (CPCs)

• Cartilage-derived stem/progenitor cells (CSPCs)

• Synovium resident multipotent progenitor cells

• Osteoblast/osteoclast resident MSCs

• Chondrogenic cells within the infrapatellar fat pad

DISEASES ADDRESSED:

• Musculoskeletal disorders

• Neurodegenerative diseases (MS, Parkinson’s, Alzheimer’s, Huntington’s, ALS, Cerebellar Ataxia)

• CNS injuries/trauma (CVA, CTE, TBI, SCI, Transverse Myelitis, Cerebellar Ataxia)

• Burns, scars, ulcers

• Heart diseases (MI, Angina, CHF)

• Lung diseases (COPD, Pulmonary Fibrosis, Interstitial Lung Disease)

• Liver and kidney diseases

• Inflammatory bowel disease (UC, Crohn’s)

• Alopecia, neuropathy/CIDP, erectile dysfunction, urinary incontinence

• Peripheral vascular disease

• Cerebral palsy, seizure disorders, autism

• Depression, bipolar disorder, drug addiction

• Type II Diabetes Mellitus, infertility, aging

EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS

• Not specifically detailed in the document.

EXOSOME CARGOS

• Cytokines: IL-10, TGF-ß3, TNFαRA, IL-1RA

• Enzymes: GAPDH, PGK, PGM, ENO, PKM2 (related to ATP-generating glycolysis)

• Growth Factors: TGFß3 (regulates cell adhesion and extracellular matrix formation)

• Nucleic Acids (RNA or DNA): IL-1RA, TIMP1 & TIMP2, TNFR1 and TNFR2, Histone Deacetylase mRNAs, GDF11, GDF15, IGFBP2, IGFBP3, IGFBP4, IGFBP6, OPG, SCFR, TGF-ß1 & TGF-ß3, VEGF, VEGFR-2, BMP4, BMP7, PTEN

• Proteins: Not specifically detailed in the document.

• Transcription Factors: Not specifically detailed in the document.

REFERENCES

• The document provides specific references (numbered) to support various claims and findings. However, a complete list of references was not provided in the sections analyzed.

 DATE OF PUBLICATION

• 2019

TITLE OF DOCUMENT

• Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response

AUTHORS

• Jia Yao, Jun Zheng, Jianye Cai, Kaining Zeng, Chaorong Zhou, Jiebin Zhang, Shihui Li, Hui Li, Liang Chen, Liying He, Huaxin Chen, Hongyuan Fu, Qi Zhang, Guihua Chen, Yang Yang, Yingcai Zhang

OVERVIEW This study investigates the therapeutic effects of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (huc-MSCs) on hepatic ischemia-reperfusion injury (IRI) in rats. It focuses on the role of these EVs in reducing hepatic apoptosis, oxidative stress, and neutrophil infiltration in hepatic tissue.

RESULTS The study found that huc-MSC-EVs protected against IRI-induced hepatic apoptosis, reduced the infiltration of neutrophils, and alleviated oxidative stress in hepatic tissue. These EVs were effective in suppressing the respiratory burst of neutrophils in vitro and prevented hepatocytes from oxidative stress-induced cell death. A key finding was that the antioxidant enzyme manganese superoxide dismutase (MnSOD), encapsulated in huc-MSC-EVs, played a significant role in reducing oxidative stress.

CELL TYPE(S)

• Human umbilical cord mesenchymal stem cells (huc-MSCs)

• Rat hepatic cells

• Neutrophils

• LO2 hepatocyte line

DISEASES ADDRESSED

• Hepatic ischemia-reperfusion injury (IRI)

EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS

• CD63

• CD9

EXOSOME CARGOS

Cytokines

• Not explicitly listed in the reviewed sections.

Enzymes

• Manganese superoxide dismutase (MnSOD)

Growth Factors

• Not explicitly listed in the reviewed sections.

Nucleic Acids (RNA or DNA)

• Not explicitly listed in the reviewed sections.

Proteins

• CD63

• CD9

• MnSOD

Transcription Factors (OSKM, Nanog)

• Not explicitly listed in the reviewed sections.

REFERENCES

• The document contains numerous references relevant to exosomes and their roles in diseases, particularly in the context of ischemia-reperfusion injury and the therapeutic potential of stem cell-derived EVs. However, specific references could not be extracted in this analysis.

 Exosome Research Publication Analysis

DATE OF PUBLICATION

• Published: August 27, 2019​​.

TITLE OF DOCUMENT

• Title: Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury​​.

AUTHORS

• Authors: Shaowei Guo, Nisim Perets, Oshra Betzer, Shahar Ben-Shaul, Anton Sheinin, Izhak Michaelevski, Rachela Popovtzer, Daniel Offen, Shulamit Levenberg​​.

OVERVIEW

• Overview: This study focuses on the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-Exo) loaded with phosphatase and tensin homolog small interfering RNA (ExoPTEN) in treating spinal cord injuries (SCI). The exosomes were administered intranasally and demonstrated the capability to cross the blood-brain barrier and target the injured spinal cord region. The treatment facilitated axonal growth and neovascularization, reduced microgliosis and astrogliosis, and significantly improved both structural and electrophysiological functions in rat models with complete SCI. This suggests potential clinical applications of intranasal ExoPTEN for SCI recovery​​.

RESULTS

• Results: The results of the study revealed that intranasal administration of ExoPTEN led to significant functional recovery in rats with complete SCI. It was observed that ExoPTEN could cross the blood-brain barrier and specifically target neurons in the injured spinal cord region. This resulted in enhanced axonal growth and reduced inflammation. ExoPTEN-treated rats showed substantial improvement in locomotor, sensory, and bladder functions compared to untreated groups. Additionally, ExoPTEN treatment reduced PTEN protein levels in the SCI area, indicating effective siRNA delivery and gene silencing​​.

CELL TYPE(S)

• Not Applicable

DISEASES ADDRESSED

• Diseases Addressed:

  • Spinal Cord Injury (SCI)​​.

EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS

• Not Applicable

EXOSOME CARGOS

• Cytokines: Not specifically mentioned.

• Enzymes: Not specifically mentioned.

• Growth Factors: Not specifically mentioned.

• Nucleic Acids (RNA or DNA): Phosphatase and Tensin Homolog small interfering RNA (ExoPTEN)​​.

• Proteins: Exosome proteins were mentioned, but specific proteins were not detailed​​.

• Transcription Factors (O,S,K,M, Nanog): Not specifically mentioned.

 Exosome Research Publication Analysis

DATE OF PUBLICATION

• Published: August 8, 2019​​.

TITLE OF DOCUMENT

• Title: Intranasally Administered Exosomes from Umbilical Cord Stem Cells Have Preventive Neuroprotective Effects and Contribute to Functional Recovery after Perinatal Brain Injury​​.

AUTHORS

• Authors: Gierin Thomi, Marianne Joerger-Messerli, Valérie Haesler, Lukas Muri, Daniel Surbek, Andreina Schoeberlein​​.

OVERVIEW

• Overview: This study investigates the effects of intranasally administered mesenchymal stromal cell (MSC)-derived exosomes on perinatal brain injury (PBI). It focuses on the neuroprotective effects of these exosomes and their potential to improve neurodevelopmental outcomes after PBI. The study demonstrates that MSC-derived exosomes can effectively reach the brain after intranasal administration and significantly reduce neuron-specific cell death in PBI, suggesting their potential as a neuroprotective strategy in perinatal brain injuries​​.

RESULTS

• Results: The study found that MSC-exosomes improved survival after PBI, effectively reached the brain after intranasal administration, and reduced gray matter injury post-PBI. Additionally, MSC-exosomes improved functional recovery, as evidenced by enhanced learning ability in animal models post-PBI. However, they did not significantly improve long-term memory impairment. Overall, the results suggest that MSC exosomes could be a valuable strategy in preventing perinatal brain injury and improving neurodevelopmental outcomes​​.

CELL TYPE(S)

• Not Applicable

DISEASES ADDRESSED

• Diseases Addressed:

  • Perinatal Brain Injury (PBI)​​.

EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS

• Not Applicable

EXOSOME CARGOS

• Cytokines: Not specifically mentioned.

• Enzymes: Not specifically mentioned.

• Growth Factors: Not specifically mentioned.

• Nucleic Acids (RNA or DNA): Not specifically mentioned.

• Proteins: Not specifically mentioned.

• Transcription Factors (O,S,K,M, Nanog): Not specifically mentioned.

[2019] Muscle‐derived miR‐34a increases with age in circulating extracellular vesicles and induces senescence of bone marrow stem cells.pdf

PDF

Exosome Research Publication Analysis

DATE OF PUBLICATION

• March 2019​​.

TITLE OF DOCUMENT

• Muscle-derived miR-34a increases with age in circulating extracellular vesicles and induces senescence of bone marrow stem cells​​.

AUTHORS

• Sadanand Fulzele​​.

OVERVIEW

• This study investigates the role of muscle-derived extracellular vesicles (EVs) and their microRNAs in aging, specifically focusing on miR-34a-5p (miR-34a). It finds that aging in mice is associated with increased miR-34a in skeletal muscle and serum-derived EVs. Muscle-derived alpha-sarcoglycan positive EVs isolated from serum samples also show a significant increase in miR-34a with age. The study demonstrates that EVs from muscle cells under oxidative stress (simulated using hydrogen peroxide) have elevated levels of miR-34a, which decreases viability and increases senescence of bone marrow mesenchymal (stromal) cells (BMSCs)​​.

RESULTS

• The study reports a significant increase in miR-34a expression in skeletal muscle and serum extracellular vesicles with aging. This increase was associated with aging inflammation and oxidative stress. In addition, EVs derived from mouse C2C12 myoblasts and human myotubes treated with hydrogen peroxide showed increased levels of miR-34a. These EVs decreased cell viability and increased cellular senescence in BMSCs. Furthermore, EVs from C2C12 cells overexpressing miR-34a significantly decreased BMSC viability and increased cellular senescence​​.

CELL TYPE(S)

• Mouse C2C12 myoblasts

• Primary human myotubes

• Bone marrow mesenchymal (stromal) cells (BMSCs)

DISEASES ADDRESSED

• Not directly addressed, but the study implicates roles in aging-related muscle and bone pathologies due to the involvement of miR-34a in muscle atrophy and myopathy, as well as its effects on BMSCs which are precursors to osteoblasts​​.

EXOSOME ENVELOPE PROTEINS and SURFACE RECEPTORS

• Alpha-sarcoglycan (SGCA)​​

EXOSOME CARGOS

• Cytokines: Not mentioned.

• Enzymes: Not mentioned.

• Growth Factors: Not mentioned.

• Nucleic Acids (RNA or DNA): miR-34a-5p (miR-34a)

• Proteins: Not specifically mentioned, but the presence of proteins in EVs is generally acknowledged.

• Transcription Factors (O,S,K,M, Nanog): Not mentioned.

 Exosome Research Publication Analysis

DATE OF PUBLICATION

• June 19, 2019​​.

TITLE OF DOCUMENT

• Preservation and Storage Stability of Extracellular Vesicles for Therapeutic Applications​​.

AUTHORS

• Anjana Jeyaram and Steven M. Jay​​.

OVERVIEW

• The paper discusses the challenges in preserving and storing extracellular vesicles (EVs) for therapeutic applications. EVs, including exosomes and microvesicles, are gaining attention for their potential as biotherapeutics and drug delivery vehicles. However, ensuring the preservation of their biological activity during storage is a significant challenge. The most promising storage method is at −80°C, but understanding the effects of storage and standardizing methods are still underdeveloped areas. These aspects are crucial for clinical translation of EV-based therapies​​.

RESULTS

• The review emphasizes the criticality of storage conditions in maintaining EV functionality. It mentions that −80°C storage is optimal for preserving isolated EV samples. However, there's a lack of comprehensive understanding regarding storage-induced changes in EV bioactivity. For EVs loaded with exogenous materials, the stability and functionality post-storage are yet to be thoroughly explored. The study highlights the need for improved storage strategies to maintain the therapeutic utility of EVs​​.

CELL TYPE(S)

• Not specifically mentioned.

DISEASES ADDRESSED

• Not specifically mentioned, but the context suggests a broad potential application in various diseases and injuries, depending on the therapeutic target of the EVs​​.

EXOSOMES ENVELOPE PROTEINS and SURFACE RECEPTORS

• Not mentioned.

EXOSOME CARGOS

• Not specifically mentioned.

 Exosome Research Publication Analysis

DATE OF PUBLICATION

• 2019

TITLE OF DOCUMENT

• Recent advances and challenges in the recovery and purification of cellular exosomes

AUTHORS

• Sergio Ayala-Mar

• Javier Donoso-Quezada

• Roberto C. Gallo-Villanueva

• Victor H. Perez-Gonzalez

• José González-Valdez

OVERVIEW: This document provides an extensive review of the current methodologies for the isolation and purification of exosomes, small vesicles secreted by various cell types. The review highlights the roles exosomes play in cellular communication and their potential as therapeutic agents for diseases like cancer and Parkinson’s. It also underscores the complexity of exosome procurement, which remains a challenge due to the intricate nature of their structure, physicochemical properties, and the need for specificity in their separation and analysis​​.

RESULTS: The document does not provide specific experimental results but rather discusses various strategies and methodologies for exosome recovery and purification. It emphasizes the importance of understanding these methods' advantages and disadvantages, especially given the potential therapeutic applications of exosomes. The review also mentions the use of exosomes as carriers for drugs and other compounds and their role in modulating pathophysiological processes, particularly in cancer therapy​​.

CELL TYPE(S):

• Eukaryotic cells, particularly those of the immune system​​

DISEASES ADDRESSED:

• Cancer

• Parkinson's disease

• Cardiovascular disease

• Neurodegenerative disorders

• Heart failure​​

EXOSOMES ENVELOPE PROTEINS and SURFACE RECEPTORS:

• Specific surface proteins (vary between cell types)

• A common set of conserved protein molecules​​

EXOSOME CARGOS:

Cytokines - Not specifically mentioned

Enzymes - Not specifically mentioned

Growth Factors - Not specifically mentioned

Nucleic Acids (RNA or DNA) - Nucleic acids​​

Proteins - Proteic cargos​​

Transcription Factors (O,S,K,M, Nanog) - Not specifically mentioned

REFERENCES:

• The document references are not specifically listed in the provided excerpts. However, it refers to various studies and methodologies throughout the text, indicating a broad base of references used for the review​​.

 You

[2019] Stem cell derived exosomes- microRNA therapy for age-related musculoskeletal disorders.pdf

PDF

Exosome Research Publication Analysis

DATE OF PUBLICATION

• 2019

TITLE OF DOCUMENT

• Stem cell derived exosomes: microRNA therapy for age-related musculoskeletal disorders

AUTHORS

• Xudong Yao, Wei Wei, Xiaozhao Wang, Li Chenglin, Mikael Björklund, Hongwei Ouyang

OVERVIEW: This paper discusses the role of stem cell (SC)-derived exosomes in treating age-related musculoskeletal disorders (MSDs). It highlights the potential of exosomes, especially those containing microRNAs (miRNAs), as therapeutic agents due to their ability to mediate cell interactions and facilitate healing in musculoskeletal tissues. The document reviews current advancements in SC technologies and the growing interest in exosomes as alternatives to direct SC therapies, which carry risks like tumorigenicity. The paper emphasizes the importance of developing standardized protocols for SC culture and exosome isolation to enable large-scale, GMP-compliant production of SC-derived exosomes​​.

RESULTS: The document outlines the therapeutic potential of SC-derived exosomal miRNAs in MSDs, with a focus on muscle and bone regeneration and osteoarthritis treatment. It discusses how miRNAs in exosomes target multiple signaling pathways and influence various processes like angiogenesis, tissue regeneration, immune regulation, and pathogen defense. The study also touches upon the challenges associated with exosome production and purification for clinical use, underscoring the need for improved biomanufacturing technologies and the importance of exosome characterization in research and therapy​​.

CELL TYPE(S):

• Hematopoietic Stem Cells (HSCs)

• Mesenchymal Stem Cells (MSCs)

• Neural Stem Cells (NSCs)

• Muscle Satellite Cells

DISEASES ADDRESSED:

• Age-related Musculoskeletal Disorders (MSDs)

• Osteoporosis

• Osteoarthritis (OA)

• Sarcopenia

EXOSOMES ENVELOPE PROTEINS and SURFACE RECEPTORS:

• Alix

• Tumor Susceptibility 101 (TSG101)

• Tetraspanins (CD9, CD63, CD81)

• Annexin A1​​

EXOSOME CARGOS:

Cytokines - Not specifically mentioned

Enzymes - Glyceraldehyde 3-phosphate dehydrogenase - Enolase - Pyruvate kinase - Metalloproteinase 9

Growth Factors - Not specifically mentioned

Nucleic Acids (RNA or DNA) - Messenger RNAs (mRNAs) - microRNAs (miRNAs) - piwi-interacting RNA - Small nucleolar RNAs - yRNAs - Vault RNAs - Small interfering RNAs (siRNAs)​​

Proteins - Heat Shock Protein 90 (HSP90) - Delta-like 4 (DLL4) - Stress-inducible protein 1 (STI1) - Wnt-10b - Oct4 - GATA4 - E-cadherin - CD34, CD71, CD133, CD142, CD235a - Angiopoietin-1 - Notch-1 - Lactoferrin - Complement 1 binding protein​​

Transcription Factors (O,S,K,M, Nanog) - Not specifically mentioned

REFERENCES:

• The document cites numerous studies, primarily focusing on the therapeutic potential and biomanufacturing of SC-derived exosomes. The references include research on miRNAs, exosomal proteins, stem cell therapies, and musculoskeletal diseases. Notably, it references pioneering work on exosome characterization, the role of exosomes in various diseases, and advancements in stem cell technology​​.

 Exosome Research Publication Analysis

DATE OF PUBLICATION

• June 25, 2019

TITLE OF DOCUMENT

• Stem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders

AUTHORS

• Milad Riazifar, M. Rezaa Mohammadi, Egest J. Pone, Ashish Yeri, Cecilia Lässer, Aude I. Segaliny, Laura L. McIntyre, Ganesh Vilas Shelke, Elizabeth Hutchins, Ashley Hamamoto, Erika N. Calle, Rossella Crescitelli, Wenbin Liao, Victor Pham, Yanan Yin, Jayapriya Jayaraman, Jonathan R. T. Lakey, Craig M. Walsh, Kendall Van Keuren-Jensen, Jan Lotvall, Weian Zhao

OVERVIEW: This document examines the use of exosomes derived from mesenchymal stem cells (MSCs) in treating autoimmune and neurodegenerative diseases, specifically focusing on multiple sclerosis. It explores the effect of MSC-produced exosomes on reducing symptoms in an experimental autoimmune encephalomyelitis (EAE) mouse model, highlighting their potential in decreasing neuroinflammation, demyelination, and enhancing the induction of regulatory T cells. The study supports the role of exosomes in modulating immune response and proposes their potential as cell-free therapies for autoimmune and central nervous system disorders​​.

RESULTS: The research demonstrates that exosomes derived from MSCs can improve functional outcomes in an EAE mouse model, reducing disease symptoms, demyelination, neuroinflammation, and promoting regulatory T cell (Treg) induction. These exosomes, particularly IFNγ-stimulated MSC-derived exosomes (IFNγ-Exo), were shown to suppress T cell activation and proliferation, reduce pro-inflammatory cytokines, and increase immunosuppressive cytokines. This suggests that MSC-derived exosomes could potentially serve as a therapeutic tool for autoimmune and neurodegenerative disorders​​.

CELL TYPE(S):

• Mesenchymal Stem Cells (MSCs)

DISEASES ADDRESSED:

• Multiple Sclerosis (MS)

• Autoimmune Disorders

• Neurodegenerative Disorders

EXOSOMES ENVELOPE PROTEINS and SURFACE RECEPTORS:

• Not specifically mentioned

EXOSOME CARGOS:

Cytokines - IL-6 - IL-12p70 - IL-17AF - IL-22

Enzymes - Indoleamine 2,3-dioxygenase (IDO)

Growth Factors - Not specifically mentioned

Nucleic Acids (RNA or DNA) - Anti-inflammatory RNAs (specific types not detailed)

Proteins - Macrophage inhibitory cytokine 1 (MIC-1) - Galectin-1 (Gal-1) - Heat shock protein 70 (HSP70) - Latent-transforming growth factor β-binding protein (LTBP)

Transcription Factors (O,S,K,M, Nanog) - Not specifically mentioned

REFERENCES:

• The document does not provide a detailed list of references. However, it refers to various studies and methodologies throughout the text, indicating a broad base of references used for the review​​​​.

 DATE OF PUBLICATION

• 2019

TITLE OF DOCUMENT

• Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients: A Prospective Phase I/II Study

AUTHORS

• Liming Wang, Shigao Huang, Shimei Li, Ming Li, Jun Shi, Wen Bai, Qianyun Wang, Libo Zheng, Yongjun Liu

OVERVIEW: This study investigates the efficacy and safety of umbilical cord mesenchymal stem cell (UC-MSC) therapy in combination with disease-modifying anti-rheumatic drugs (DMARDs) for treating rheumatoid arthritis (RA). RA is a chronic autoimmune disease affecting joints, which leads to pain, swelling, and eventually joint stiffness, malformation, and loss of function. Traditional treatments, including NSAIDs, DMARDs, and immunosuppressants, have limitations. This study explores the potential of UC-MSCs to mitigate these limitations through their regenerative and immunomodulatory properties​​.

RESULTS: The study demonstrates long-term safety and efficacy of UC-MSC therapy combined with DMARDs in treating RA. Over three years, UC-MSC treatment showed consistent efficacy in alleviating RA symptoms, reducing HAQ and DAS28 scores, and decreasing levels of RF, CRP, ESR, and anti-CCP. The treatment did not present significant adverse effects, and only a few patients exhibited mild, transient symptoms like flu-like symptoms during infusion. The combined therapy of UC-MSCs and DMARDs improved the quality of life for RA patients, suggesting that UC-MSC therapy can be a viable and safe treatment option for RA​​.

CELL TYPE(S):

• Umbilical Cord Mesenchymal Stem Cells (UC-MSCs)

DISEASES ADDRESSED:

• Rheumatoid Arthritis (RA)

EXOSOMES ENVELOPE PROTEINS and SURFACE RECEPTORS:

• Not specifically mentioned

EXOSOME CARGOS:

Cytokines - Not specifically mentioned

Enzymes - Not specifically mentioned

Growth Factors - Not specifically mentioned

Nucleic Acids (RNA or DNA) - Not specifically mentioned

Proteins - Not specifically mentioned

Transcription Factors (O,S,K,M, Nanog) - Not specifically mentioned

REFERENCES:

• The document refers to various studies and methodologies throughout the text, indicating a broad base of references used for the review. However, specific references are not detailed in the provided excerpts​​​​.