TY - JOUR

T1 - Limited Potential or Unfavorable Manipulations?

T2 - Strategies Toward Efficient Mesenchymal Stem/Stromal Cell Applications

AU - Lavrentieva, Antonina

AU - Hoffmann, Andrea

AU - Lee-Thedieck, Cornelia

N1 - Funding information: This work has been carried out within the framework of the SMART BIOTECS alliance between the Technische Universität Braunschweig and the Leibniz Universität Hannover. This initiative is supported by the Ministry of Science and Culture (MWK) of Lower Saxony, Germany. CL-T has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (Grant Agreement No. 757490). AL research is supported by German Research Foundation (DFG Project 398007461 488 “3D Dual-Gradient Systems for Functional Cell Screening”). AH acknowledges funding by the German Research Foundation with the research unit FOR 2180 “Graded Implants for Tendon-Bone Junctions.” The publication of this article was funded by the Open Access Fund of the Leibniz Universität Hannover. Funding.

PY - 2020/5/19

Y1 - 2020/5/19

N2 - Despite almost 50 years of research and over 20 years of preclinical and clinical studies, the question of curative potential of mesenchymal stem/stromal cells (MSCs) is still widely discussed in the scientific community. Non-reproducible treatment outcomes or even absence of treatment effects in comparison to control groups challenges the potential of these cells for routine application both in tissue engineering and in regenerative medicine. One of the reasons of such outcomes is non-standardized and often disadvantageous ex vivo manipulation of MSCs prior therapy. In most cases, clinically relevant cell numbers for MSC-based therapies can be only obtained by in vitro expansion of isolated cells. In this mini review, we will discuss point by point possible pitfalls in the production of human MSCs for cell therapies, without consideration of material-based applications. Starting with cell source, choice of donor and recipient, as well as isolation methods, we will then discuss existing expansion protocols (two-/three-dimensional cultivation, basal medium, medium supplements, static/dynamic conditions, and hypoxic/normoxic conditions) and influence of these strategies on the cell functionality after implantation. The role of potency assays will also be addressed. The final aim of this mini review is to illustrate the heterogeneity of current strategies for gaining MSCs for clinical applications with their strengths and weaknesses. Only a careful consideration and standardization of all pretreatment processes/methods for the different applications of MSCs will ensure robust and reproducible performance of these cell populations in the different experimental and clinical settings.

AB - Despite almost 50 years of research and over 20 years of preclinical and clinical studies, the question of curative potential of mesenchymal stem/stromal cells (MSCs) is still widely discussed in the scientific community. Non-reproducible treatment outcomes or even absence of treatment effects in comparison to control groups challenges the potential of these cells for routine application both in tissue engineering and in regenerative medicine. One of the reasons of such outcomes is non-standardized and often disadvantageous ex vivo manipulation of MSCs prior therapy. In most cases, clinically relevant cell numbers for MSC-based therapies can be only obtained by in vitro expansion of isolated cells. In this mini review, we will discuss point by point possible pitfalls in the production of human MSCs for cell therapies, without consideration of material-based applications. Starting with cell source, choice of donor and recipient, as well as isolation methods, we will then discuss existing expansion protocols (two-/three-dimensional cultivation, basal medium, medium supplements, static/dynamic conditions, and hypoxic/normoxic conditions) and influence of these strategies on the cell functionality after implantation. The role of potency assays will also be addressed. The final aim of this mini review is to illustrate the heterogeneity of current strategies for gaining MSCs for clinical applications with their strengths and weaknesses. Only a careful consideration and standardization of all pretreatment processes/methods for the different applications of MSCs will ensure robust and reproducible performance of these cell populations in the different experimental and clinical settings.

KW - bioreactor

KW - donor variability

KW - expansion protocols

KW - mesenchymal stem/stromal cell

KW - potency

UR - http://www.scopus.com/inward/record.url?scp=85085891637&partnerID=8YFLogxK

U2 - 10.3389/fcell.2020.00316

DO - 10.3389/fcell.2020.00316

M3 - Review article

C2 - 32509777

AN - SCOPUS:85085891637

VL - 8

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

M1 - 316

ER -