Therapeutic Use of Mesenchymal Stromal Cells: The Need for Inclusive Characterization Guidelines to Accommodate All Tissue Sources and Species

Abstract

Following their discovery over 50 years ago, mesenchymal stromal cells (MSCs) have become one of the most studied cellular therapeutic products by both academia and industry due to their regenerative potential and immunomodulatory properties. The promise of MSCs as a therapeutic modality has been demonstrated by preclinical data yet has not translated to consistent, successful clinical trial results in humans. Despite the disparities across the field, MSC shareholders are unified under one common goal—to use MSCs as a therapeutic modality to improve the quality of life for those suffering from a malady in which the standard of care is suboptimal or no longer effective. Currently, there is no Food and Drug Administration (FDA)-approved MSC therapy on the market in the United States although several MSC products have been granted regulatory approval in other countries. In this review, we intend to identify hurdles that are impeding therapeutic progress and discuss strategies that may aid in accomplishing this universal goal of widespread therapeutic use.

When Origin Matters: Properties of Mesenchymal Stromal Cells From Different Sources for Clinical Translation in Kidney Disease

“…Expression of other markers such as CD71, CD146, CD106, and CD274 has been shown to be heterogeneous, and in some cases correlates with donor age ( 53 ). Adhesion molecules such as CD44 (hyaluronic acid receptor) or CD29 (integrin β1 receptor) are highly expressed in human MSCs and have been recently proposed to be included in characterization panels ( 266 ). However, expression of markers such as CD146, another key adhesion molecule, can vary between sources, being highly expressed in UC-MSCs compared with BM-MSCs ( 230 , 237 , 240 , 264 ) and subcutaneous AT-MSCs ( 267 ).…”

Immunomodulatory Effects of Mesenchymal Stem Cells on Drug-Induced Acute Kidney Injury

“…MSCs can easily expand in vitro into high numbers in a short period of time. This is an important prerequisite for MSCs that are widely used in experimental research and clinical practice, including AKI treatment (33). Moreover, MSCs can be cultured from adipose tissue, cord blood, umbilical cord, placenta, and fetal lungs.…”

Biomaterials and Adipose-Derived Mesenchymal Stem Cells for Regenerative Medicine: A Systematic Review

“…Bone marrow (BM) is a widely known and used source of MSC, but it can be obtained from several adult tissues. For instance, adipose tissue (AT) is another great source of MSC and also dental tissues, extra-embryonic tissues (such as amniotic fluid, amniotic membrane, fetal membrane and placenta), endometrium and Wharton’s jelly [ 12 , 13 ]. The procedure to obtain stem cells from BM is very invasive and painful.…”

“…The procedure to obtain stem cells from BM is very invasive and painful. On the other hand, the harvesting process of adipose-derived stem cells (AD-MSCs) is fairly simple, considering that liposuction and bichectomy surgery waste material contain these cells [ 13 ]. Buccal fat pad (BFP), which can be obtained from bichectomy surgery, are cells phenotypically similar to AD-MSCs obtained from liposuction surgery [ 14 ].…”

“…It is also known that the concentration of AD-MSCs in adipose tissue is almost five hundred times the concentration of BM-MSC in bone marrow [ 15 ]. In conclusion, AD-MSC and BFP are promising sources of MSC, due to their easy harvest and for being a source of stem cells of great value [ 13 , 14 ]. In addition, they have prominent implications in tissue regeneration due to their ability to differentiate into multiple lineages and to secrete various cytokines, as well as having immunomodulatory effects [ 16 ].…”