Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review

Abstract

Summary Identified 50 years ago, mesenchymal stromal/stem cells (MSCs) immediately generated a substantial interest among the scientific community because of their differentiation plasticity and hematopoietic supportive function. Early investigations provided evidence of a relatively low engraftment rate and a transient benefit for challenging congenital and acquired diseases. The reasons for these poor therapeutic benefits forced the entire field to reconsider MSC mechanisms of action together with their ex vivo manipulation procedures. This phase resulted in advances in MSCs processing and the hypothesis that MSC‐tissue supportive functions may be prevailing their differentiation plasticity, broadening the spectrum of MSCs therapeutic potential far beyond their lineage‐restricted commitments. Consequently, an increasing number of studies have been conducted for a variety of clinical indications, revealing additional challenges and suggesting that MSCs are still lagging behind for a solid clinical translation. For this reason, our aim was to dissect the current challenges in the development of still promising cell types that, after more than half a century, still need to reach their maturity. Stem Cells Translational Medicine 2019;8:1135–1148

Challenges and translational considerations of mesenchymal stem/stromal cell therapy for Parkinson’s disease

“…Variability can stem from different injection sites within the same sources, or aspiration techniques, which can influence cell yield, viability, and differentiation potential 59,60 . Compared with AD and UC, harvesting BM is the most invasive and can cause the most pain and infection risk 78,79 . BM aspirate contains only 0.001-0.01% MSCs in the overall cell population, which translates to roughly 60-600 cells/ mL of aspirate 76 .…”

Ginsenoside Rg1 as an Effective Regulator of Mesenchymal Stem Cells

“…These cells can differentiate into adipocytes, osteoblasts, and chondrocytes in vitro and in vivo and secrete various anti-inflammatory cytokines and exosomes in different microenvironments (Chamberlain et al, 2007;Phinney and Pittenger, 2017). MSCs can be derived from many connective tissues and organ stroma, including bone marrow, Wharton's jelly of the umbilical cord, umbilical cord blood, adipose tissue, dental pulp, and periodontal tissues (Alison et al, 2000;Mastrolia et al, 2019). Meanwhile, these cells exhibit a fibroblastic morphology, adhere to a plastic surface when cultured in vitro, and share a common immunophenotype consisting of positive CD105, CD73, and CD90 expression and negative CD45, CD34, CD14, CD19, and HLA-DR expression (Wagers and Weissman, 2004).…”

Exosome therapeutics for lung regenerative medicine

“…However, exosome isolation in large-scale applications remains impractical, with structural damage and batch inconsistencies hindering clinical translation. Although solutions such as higher resolution density gradients would help produce purer batches, they are not a feasible approach for large-scale production and GMP standards, due to discrepancies in successful isolation and retained quality [62]. Systems such as tangential flow filtration (TFF) have been developed to combat such limitations, assuring more efficient exosome yields and decreased vesicular damage [63].…”