Mesenchymal Stem/Progenitor Cells: The Prospect of Human Clinical Translation

Abstract

Mesenchymal stem/progenitor cells (MSCs) are key players in regenerative medicine, relying principally on their differentiation/regeneration potential, immunomodulatory properties, paracrine effects, and potent homing ability with minimal if any ethical concerns. Even though multiple preclinical and clinical studies have demonstrated remarkable properties for MSCs, the clinical applicability of MSC-based therapies is still questionable. Several challenges exist that critically hinder a successful clinical translation of MSC-based therapies, including but not limited to heterogeneity of their populations, variability in their quality and quantity, donor-related factors, discrepancies in protocols for isolation, in vitro expansion and premodification, and variability in methods of cell delivery, dosing, and cell homing. Alterations of MSC viability, proliferation, properties, and/or function are also affected by various drugs and chemicals. Moreover, significant safety concerns exist due to possible teratogenic/neoplastic potential and transmission of infectious diseases. Through the current review, we aim to highlight the major challenges facing MSCs’ human clinical translation and shed light on the undergoing strategies to overcome them.

Biomimetic Mineralization Promotes Viability and Differentiation of Human Mesenchymal Stem Cells in a Perfusion Bioreactor

“…In fact, a clear trend for upregulation of genes related to osteogenic commitment of primary hMSC cultured in mineralized scaffolds (RCP.MgAp) when compared with non-modified scaffolds (RCP) was observed. Despite this trend, no statistically significant differences in the expression of the tested genes were observed due to variations between donors, a fact widely reported and accepted in the literature for primary cells derived from different patients [ 57 ]. Moreover, the presence of osteogenic factors (L-ascorbic acid, dexamethasone and β-glycerophosphate) also induced dramatic differences in levels of bone-specific gene induction in hMSC exposed to osteo-inductive media, as previously reported by Donald G. Phinney et al [ 58 ].…”

Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell–Extracellular Matrix Interactions

“…Regarding the gene expression analysis ( Figure 7 ), large donor-specific variations were observed due to the primary origin of hMSCs. Donor-to-donor differences are widely reported in the literature in various contexts, recognized to be a reflection of not only the age or overall health of the donor, but also of the diversity of environments from which hMSCs may be isolated [ 37 , 38 ].…”

Cell-Based Transplantation versus Cell Homing Approaches for Pulp-Dentin Complex Regeneration

“…Regenerative dentistry is no longer a dream, thanks to the current efforts to imply stem/progenitor cell-based techniques to enhance the regeneration of the pulp-dentin complex and to replace conventional endodontic pulp therapy. Yet, such novel therapies dictate careful testing first in vitro and in animal models, prior to human clinical translation [ 150 ]. Cell-based therapies still face many challenges, mainly economical and ethical concerns.…”