Abstract
The intense research focus on stem and progenitor cells could be attributed to their differentiation potential to generate new cells to replace diseased or lost cells in many highly intractable degenerative diseases, such as Alzheimer disease, multiple sclerosis, and heart diseases. However, experimental and clinical studies have increasingly attributed the therapeutic efficacy of these cells to their secretion. While stem and progenitor cells secreted many therapeutic molecules, none of these molecules singly or in combination could recapitulate the functional effects of stem cell transplantations. Recently, it was reported that extracellular vesicles (EVs) could recapitulate the therapeutic effects of stem cell transplantation. Based on the observations reported thus far, the prevailing hypothesis is that stem cell EVs exert their therapeutic effects by transferring biologically active molecules such as proteins, lipids, mRNA, and microRNA from the stem cells to injured or diseased cells. In this respect, stem cell EVs are similar to EVs from other cell types. They are both primarily vehicles for intercellular communication. Therefore, the differentiating factor is likely due to the composition of their cargo. The cargo of EVs from different cell types are known to include a common set of proteins and also proteins that reflect the cell source of the EVs and the physiological or pathological state of the cell source. Hence, elucidation of the stem cell EV cargo would provide an insight into the multiple physiological or biochemical changes necessary to affect the many reported stem cell-based therapeutic outcomes in a variety of experimental models and clinical trials.
Highlights
Stem cells or progenitor cells are presently our best candidate therapeutic to treat intractable degenerative or genetic diseases through their capacity to engraft, differentiate, and generate new healthy cells to replace injured or diseased cells
The discovery of pluripotent stem cell (PSC) and non-hematopoietic tissue stem cells such as mesenchymal stem cell (MSC), neural stem cell (NSC), endothelial progenitor cell (EPC), or cardiac progenitor cells (CPC) has generated much optimism that non-hematopoietic diseases could be treated by replacing diseased cells with newly generated cells from pluripotent or tissue stem cells
We subsequently reported that the smaller MSC-derived exosomes with a hydrodynamic radius of 55–65 nm protect against acute myocardial ischemia/reperfusion injury [38,47], enhance wound healing [48], alleviate graft-versus-host disease (GVHD) [49], reduce renal injury [50], and promote damaged hepatic regeneration [51]
Summary
Stem cells or progenitor cells are presently our best candidate therapeutic to treat intractable degenerative or genetic diseases through their capacity to engraft, differentiate, and generate new healthy cells to replace injured or diseased cells. This is best evidenced by the clinical success of hematopoietic stem cells as used in bone marrow transplantation to re-populate the recipient’s hematopoietic compartment with donor cells and treat a myriad of diseases such as cancer and genetic blood diseases such as thalassemia. Many of these stem or progenitor cells are being tested in clinical trials to treat many different diseases such as acute myocardial infarction (AMI), liver damage, ischemic kidney failure or stroke, amyotrophic lateral sclerosis (ALS), spinal cord injury, graft-versus-host disease (GVHD), etc. (Available online: http://www.clinicaltrials.gov)
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