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WO-2026096838-A1 - TREATMENT OF ORGAN DYSFUNCTION USING A COMBINATION OF MESENCHYMAL STEM CELLS AND EXOSOMES

WO2026096838A1WO 2026096838 A1WO2026096838 A1WO 2026096838A1WO-2026096838-A1

Abstract

Embodiments relate to a method of treating a disease or condition in a subject in need thereof, the method comprising: administering a therapeutic effective amount of a pharmaceutical composition comprising mesenchymal cells and exosomes to the subject; wherein the mesenchymal cells and exosomes are in a ratio of about 1: 2500 to 1: 250000; wherein the mesenchymal cells have a stemness quality more than 90% and viability more than 95%, and the exosomes are free of a cellular contaminant as detected by immunoblotting technique, wherein the cellular contaminant comprises calnexin, and treating said disease or condition.

Inventors

  • ATLURI, Sairam

Assignees

  • STEMCURES

Dates

Publication Date
20260507
Application Date
20251031
Priority Date
20251031

Claims (20)

  1. 1. A method of treating a disease or a condition in a subject in need thereof, the method comprising: administering a therapeutic effective amount of a pharmaceutical composition comprising mesenchymal cells and exosomes to the subject; wherein the mesenchymal cells and exosomes are in a ratio of about 1 : 2500 to 1: 250000 wherein the mesenchymal cells have a sternness quality more than 90% and viability more than 95%, and the exosomes are free of a cellular contaminant as detected by immunoblotting technique, wherein the cellular contaminant comprises calnexin, and treating said disease or condition.
  2. 2. The method of claim 1, wherein the cellular contaminant further comprises GM130.
  3. 3. The method of claim 1, wherein the exosomes have a zeta potential in a range of -30mV to -50 mV, and a size range between 85 nm to 130 nm as measured using the ZetaView system by Particle Metrix.
  4. 4. The method of claim 1, wherein a ratio of the mesenchymal cells to exosomes is 1: 150,000.
  5. 5. The method of claim 1, wherein a ratio of the mesenchymal cells to exosomes is 1:75,000.
  6. 6. The method of claim 1, wherein a ratio of the mesenchymal cells to exosomes is 1: 10,000.
  7. 7. The method of claim 1, wherein a ratio of the mesenchymal cells to exosomes is 1:5000.
  8. 8. The method of claim 1, further comprising administering peripheral blood mononuclear cells along with the mesenchymal cells and the exosomes.
  9. 9. The method of claim 1, wherein said disease or condition is selected from a neurological disease, a muscular disease, an autoimmune disease, an inflammatory disease, a digestive disease, an energy homeostasis disease, a fibrotic disease, aging, radiation induced injury, cell transplant rejection and a proliferative disease.
  10. 10. The method of claim 1 or 9, wherein the disease is a fibrotic disease.
  11. 11. The method of claim 10, wherein the fibrotic disease comprises a liver fibrosis.
  12. 12. The method of claim 1, wherein the mesenchymal cells are derived from umbilical cord of a mammal. Attorney Docket No. SASC-OOl-OIWO
  13. 13. The method of claim 1 to 3, wherein the pharmaceutical composition is configured to improve the liver morphology by more than 80% as detected by H&E staining.
  14. 14. The method of claim 1 or 3, wherein the exosomes are derived from the mesenchymal cells.
  15. 15. The method of claim 1, wherein said administering comprises at least one of intravenous administration, intramuscular administration, intranasal administration, intrathecal administration, intrastriatal administration, intracranial administration, intraarterial administration, and subcutaneous administration.
  16. 16. The method of claim 1 to 3, wherein the pharmaceutical composition is configured to improve the liver morphology by more than 80% as detected by H&E staining.
  17. 17. The pharmaceutical composition of claim 1 to 3, wherein the pharmaceutical composition is configured to increase Treg cells by more than 20%.
  18. 18. The method of claim 1 to 3, wherein the pharmaceutical composition is configured to inhibit a lymphocyte proliferation by more than 85% in the subject having a fibrotic disease.
  19. 19. The method of claim 1, wherein the mesenchymal cells have population doubling time (PDT) about 23 hours or less without any addition of a growth stimulant.
  20. 20. The method of claim 1 to 3, wherein the exosomes have biomarkers selected from CD9, TSG101, and/or HSP70 having expression level more than 95%, and enriched by miRNA selected from miR-125a-3p, miR-146a, and/or miR-133.

Description

Attorney Docket No. SASC-OOl-OIWO TREATMENT OF ORGAN DYSFUNCTION USING A COMBINATION OF MESENCHYMAE STEM CEELS AND EXOSOMES CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit under 35 U.S.C §119 of U.S. Provisional Application No. 63/714,195, filed on October 31, 2024, titled “Human Umbilical Cord-Derived Mesenchymal Stem Cells in combination with Small Extracellular Vesicles Improve Survival and Dramatically Reduce Fibrosis and Cirrhosis in Wistar Rats receiving Ccl4”, which is/arc hereby incorporated by reference in its entirety. TECHNICAL FIELD [0002] This disclosure relates to a pharmaceutical composition having mesenchymal cells and exosomes. In particular, this disclosure relates to a pharmaceutical composition having mesenchymal cells and exosomes derived from it. In some embodiment, the disclosure also relates to use of the composition in treatment of a disease in a mammal. In some embodiment, the disclosure also relates to method of isolating of mesenchymal stem cells and exosomes. BACKGROUND [0003] Currently, there are numerous medical conditions that have limited treatment options. Innovative biological products including stem cells have the potential to fill this therapeutic void. Stem cells possess the remarkable capability to repair and regenerate damaged tissues and organs, offering new hope for patients with previously untreatable conditions. [0004] Stem cells are capable of regenerating damaged tissues as they possess immunomodulatory, anti-inflammatory, anti-apoptotic, antifibrotic and neovascularization capabilities. By leveraging the powers bestowed by nature on stem cells, stem cell therapy can be seen as a “natural” way of treating diseases. A single stem cell product is a broad-spectrum drug that is capable of treating various medical conditions. Introducing stem cells into the body could be treated akin to infusing intelligence as stem cells are known to diagnose the medical condition and “custom” secrete different growth factors, cytokines and chemokines that repair the affected organ. Most importantly, numerous clinical trials involving several thousands of patients have established the safety of stem cells. [0005] Extensive animal studies and preliminary data suggest that stem cells can treat numerous conditions not limited to lower back pain, joint degeneration, stroke injury, heart failure, kidney failure, various degenerative neurological conditions, chronic obstructive pulmonary disease, CO VID infection, Crohn’s disease, peripheral vascular disease and autoimmune diseases. [0006] However, unlike small chemical entity drugs, stem cells are very complex. The large-scale Attorney Docket No. SASC-OOl-OIWO production of stem cells can be challenging, and the method adopted for producing stem cells affects not only stem cell yield but also their quality. There is a need in the art for improved stem cells as well as for improved methods for preparing stem cells that achieve a high yield of stem cells and are cost-effective. There is also a need in the art for methods that yield stem cells with improved properties. [0007] Mesenchymal stromal cells, also called mesenchymal stem cells (MSCs), are a type of adult stem cells that can be easily manipulated in vitro conditions. Stem cells present in early embryonic stages are pluripotent, whereas MSCs exhibit more limited plasticity, differentiating mainly into osteoblasts, adipocytes and chondrocytes (mesodermal cells) and to some extent also to skeletal muscle and endothelial cells. MSCs are present in the bone marrow and adipose tissue, and are also present in peripheral blood, placenta, umbilical cord blood, dental pulp, and other tissues. [0008] MSCs secrete a plethora of biologically active proteins (Id., citing Tremain N, et al. Stem Cells 2001 ; 19: 408-418; Phinney D G, et al. Stem Cells 2006; 24: 186-198; Ren J, et al. Cytotherapy 2011; 13: 661-674). [0009] High performance liquid chromatography (HPTC) and dynamic light scatter (DLS) analyses revealed that MSCs secrete cardioprotective microparticles with a hydrodynamic radius ranging from 30-150nm (Id., citing Chen et al., 2011 ; Tai et al. J. Mol. Cell. Cardiol. (2010) 48: 1215-1224). [0010] MSC-derived EVs, which include exosomes and microvesicles (MV), are involved in cell- to-cell communication, cell signaling, and altering cell or tissue metabolism at short or long distances in the body, and can influence tissue responses to injury, infection, and disease (Phinney, D G and Pittenger, M F. Stem Cells (2017) 35: 851-58). Their content includes cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs (Id.). The content of MSC EVs is not static; they are a product of the MSC tissue origin, its activities, and the immediate intercellular neighbors of the MSCs (Id.). [0011] Although MSC-derived EVs recapitulate to a large extent the immensely broad therapeutic effects previously attributed to MSCs, most studies fall short of