Mesenchymal Stem Cell Therapy
Mesenchymal Stem Cells or Multipotent Mesenchymal Stromal Cells (collectively referred to as MSCs) are currently being tested in a number of clinical trials for various diseases including graft-versus-host disease, Crohn’s disease, myocardial infarction,
- PDF / 531,456 Bytes
- 23 Pages / 439.37 x 666.14 pts Page_size
- 96 Downloads / 230 Views
Mesenchymal Stem Cell Exosomes: The Future MSC-Based Therapy? Ruenn Chai Lai, Ronne Wee Yeh Yeo, Soon Sim Tan, Bin Zhang, Yijun Yin, Newman Siu Kwan Sze, Andre Choo, and Sai Kiang Lim
Abstract The ease of isolation from adult tissues, large ex vivo expansion capacity, and apparent therapeutic efficacy in a wide range of disease indications have made mesenchymal stem cells (MSCs) the stem cell of choice for regenerative medicine. Clinical and animal studies have demonstrated that secreted trophic factors, and not stem cell differentiation, likely mediated much of the therapeutic efficacy of MSCs. This paradigm shift in the therapeutic mechanism of MSCs has started to transform MSC therapy from a cell- to biologic-based therapy. Our group has identified the exosome, a secreted membrane vesicle, as an active therapeutic factor in MSC secretion. An exosome is thought to mediate cell to cell communication. It carries a large and varied protein cargo that could regulate a wide array of biochemical and cellular processes. These include enhancing glycolysis which increases not only cellular ATP production but also glycolytic intermediates for anabolic activities, inducing adenosine-mediated activation of survival kinases (e.g., ERK and AKT via
R.C. Lai • S.S. Tan • B. Zhang • Y. Yin Institute of Medical Biology, A*STAR, Singapore R.W.Y. Yeo Institute of Medical Biology, A*STAR, Singapore National University of Singapore, Graduate School for Integrative Sciences and Engineering, Buona Vista, Singapore N.S.K. Sze School of Biological Sciences, Nanyang Technological University, Singapore A. Choo Bioprocessing Technology Institute, A*STAR, Singapore S.K. Lim (*) Institute of Medical Biology, A*STAR, Singapore Department of Surgery, YLL School of Medicine, Singapore, NUS, Singapore e-mail: [email protected] L.G. Chase and M.C. Vemuri (eds.), Mesenchymal Stem Cell Therapy, Stem Cell Biology and Regenerative Medicine, DOI 10.1007/978-1-62703-200-1_3, © Springer Science+Business Media New York 2013
39
40
R.C. Lai et al.
CD73) and reducing complement activation through CD59. As these processes are fundamental, non-tissue specific processes in ameliorating tissue injury and promoting tissue repair, MSC exosomes could potentially underpin the therapeutic efficacy of MSC in diverse disease indications. This could transform present MSCbased therapies into MSC exosome-based therapies. Keywords Mesenchymal stem cells • Exosome • Proteome • Glycolysis • Ecto-5¢ nucleotidase • Complement-mediated cell lysis • Therapy
3.1
Background
Mesenchymal stem cells (MSCs) were first described in 1968 as a population of multipotent fibroblast-like cells that reside in the bone marrow and have the potential to differentiate into osteocytes, chondrocytes, adipocytes, and myoblasts [1]. Since then MSCs have been isolated from adipose tissue [2, 3], liver [4], muscle [5], amniotic fluid [6], placenta [7, 8], umbilical cord blood [2], dental pulp [9, 10], and other sources [4, 11]. Their differentiation potential has also expanded in
Data Loading...
