Research and Development

Besides manufacturing clinical grade stem cells, SBS pursues research and development in the domain of stem cells in order to create new cell therapy based modalities for human medical use. Adipose tissue derived stem cells (ADSCs) are self renewing cells that can differentiate to many other cell types. This makes ADSCs attractive starting material for developing cell based treatments for regenerative medicine applications. After transplantation the engrafted multipotent stem cells differentiate into different cell types and regenerate the damaged tissue. Alternatively, some secretomes of transplanted stem cells stimulates the endogenous stem cells that repair the damaged cells. This signaling from one cell to another is called the paracrine effect; the action of the secretion of one kind of cell on another kind. In fact paracrine effect acts by regenerating the damaged host tissue without direct engrafting of the the transplanted cells. Many different cell types, including adipose tissue derived stem cells, can invoke a paracrine response that result in activation of host stem cells after transplantation.

SBS’ research program is based on utilisation of the paracrine effect of stem cells. Our own experimental results and many other researchers’ show that paracrine effect is a major component of the regenerative effect of transplanted stem cells. Paracrine effect is exerted via secretomes of stem cells. A major component of the secretomes are Extracellular Vesicles (EVs).

Copyright Graça R., et al. 2013

Extracellualr Vesicles (EVs):

  • EVs are small cargo-carrying vesicles released by cells into the extracellular space,
  • EVs are membrane bound particles packed with cytokines, regulatory proteins, DNA and RNAs,
  • EV load can be changed for specific purpose by pre-conditioning the stem cells,
  • Unlike live cells, EV-based products do not have the limitations of storage,
  • EV-based products can be stored as off-the-shelf products,
  • Diagnostic and therapeutic potentials of EVs are the subject of many research programs at many centres including ours.

SBS is currently involved in research on developing EV-based products for the treatment of

  • Psoriasis
  • Antiageing
  • Arthritis
  • Chronic wounds

Independent Publications about EVs:

Lin L. and Du L., The role of secreted factors in stem cells-mediated immune regulation. Cellular Immunology (2018) 326:24

Phan J et al. , Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell-free therapy. Journal of Extracellular Vesicles (2018) 7:1

Pomatto M. A. C. et al, Noncoding RNAs Carried by Extracellular Vesicles in Endocrine Diseases. International Journal of Endocrinology  (2018) Article ID 4302096

Venkat P. et al, Cell-Based and Exosome Therapy in Diabetic Stroke. Stem Cells translational Medicine (2018) 7:451

Lu et al. Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells. Stem Cell Research & Therapy (2017) 8:108

Chen B. et al, Stem Cell-Derived Extracellular Vesicles as a Novel Potential Therapeutic Tool for Tissue Repair. Stem Cells Translational Medicine (2017) 6:1753

Doeppner T.R., Concise Review: Extracellular Vesicles Overcoming Limitations of Cell Therapies in Ischemic Stroke. Stem Cells Translational Medicine (2017)

Mead, B. and  Tomarev, S., Bone Marrow-Derived Mesenchymal Stem Cells-Derived Exosomes Promote Survival of Retinal Ganglion Cells Through miRNA-Dependent Mechanisms. Stem Cells Transl Med. (2017) 6:1273

Phinney D.G. and Pitteger M., Concise Review: MSC-Derived Exosomes for Cell-Free Therapy. Stem Cells Express (2017) 35:851

Wang J. et al. Role of mesenchymal stem cells, their derived factors, and extracellular vesicles in liver failure. Stem Cell Research & Therapy (2017) 8:137

Willis G. R. et al, Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for Purpose Potency. Hypothesis and Theory 09 October (2017) doi: 10.3389/fcvm.2017.00063

Wu H-H. and Lee O.K.,  Exosomes from mesenchymal stem cells induce the conversion of hepatocytes into progenitor oval cells. Stem Cell Research & Therapy (2017) 8:117

Bell B. et al, Designer exosomes as next-generation cancer immunotherapy. Nanomedicine: Nanotechnology, Biology, and Medicine (2016) 12: 163

Kim, D. et al. Chromatographically isolated CD63+CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI. PNAS (2016) 113: 170

Onzi G. R., Analysis of the safety of mesenchymal stromal cells secretome for glioblastoma treatment. Cytotherapy, (2016) 18: 828

Raj Kishore R. and Khan M.,  More Than Tiny Sacks: Stem Cell Exosomes as Cell-Free Modality for Cardiac Repair. Circ Res . (2016) 118:330

Thind  A. Wilson C. Exosomal miRNAs as cancer biomarkers and therapeutic targets, Journal of Extracellular Vesicles (2016) 5: 31292

Headland S.E. et al, Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Rheumatoid Arthritis (2015) 7: 1

Kim H. O. et al, Mesenchymal Stem Cell-Derived Secretome and Microvesicles as a Cell-Free Therapeutics for Neurodegenerative Disorders. Tissue Engineering and Regenerative Medicine (2013) 10: 93

Li T., Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Liver Fibrosis. Stem Cells and Development (2013) 22, 6:845

Mokarizadeh A., Mesenchymal stem cell derived microvesicles: Trophic shuttles forenhancement of sperm quality parameters. Reproductive Toxicology (2013) 42: 78

Yeo R. W. Y., Exosome: A Novel and Safer Therapeutic Refinement of Mesenchymal Stem Cell. Exosomes and Microvesicles (2013) 1, 7

Zimmerlin L., Mesenchymal stem cell secretome and regenerative therapy after cancer. Biochimie (2013):11

Lopatina T. et al, Stem Cell-Derived Microvesicles: A Cell Free Therapy Approach to the

Regenerative Medicine.  Current Biotechnology (2012) 1: 11

Ranganath S.H. et al,  Harnessing the Mesenchymal Stem Cell Secretome for the Treatment of Cardiovascular Disease. Cell Stem Cell (2012) 10: 244

Li C. et al, Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen. Med. (2011) 6(4): 481

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