TY - JOUR
T1 - Predicting and Promoting Human Bone Marrow MSC Chondrogenesis by Way of TGFβ Receptor Profiles
T2 - Toward Personalized Medicine
AU - Rothweiler, René
AU - Basoli, Valentina
AU - Duttenhoefer, Fabian
AU - Kubosch, David
AU - Schmelzeisen, Rainer
AU - Johnstone, Brian
AU - Alini, Mauro
AU - Stoddart, Martin James
N1 - Publisher Copyright:
© Copyright © 2020 Rothweiler, Basoli, Duttenhoefer, Kubosch, Schmelzeisen, Johnstone, Alini and Stoddart.
PY - 2020/6/26
Y1 - 2020/6/26
N2 - The use of human mesenchymal stromal cells (hMSCs) for cartilage regeneration has been hampered by the inherent donor variation of primary monolayer expanded cells. Although CD markers are typically used to characterize cell populations, there is no correlation between CD marker profile and functional outcomes. Therefore, we aimed to discover novel predictive MSC chondrogenesis markers. The chondrogenic potential of primary human bone marrow MSCs (hBMSCs) over multiple passages was assessed by standard pellet culture. We confirmed that the ratio of TGFβ-RI/TGFβ-RII at the time of cell recovery from the tissue culture plastic reliably predicted chondrogenic potential. Furthermore, it is possible to prospectively characterize any human BMSC cell population as responders or non-responders with respect to chondrogenic differentiation potential. Transient increase of the ratio with siRNA knockdown of TGFβ-RII reproducibly recovered the chondrogenic differentiation ability of non-responsive MSCs. Together this offers an opportunity to produce a more functionally characterized cell population for use in autologous cartilage repair therapies.
AB - The use of human mesenchymal stromal cells (hMSCs) for cartilage regeneration has been hampered by the inherent donor variation of primary monolayer expanded cells. Although CD markers are typically used to characterize cell populations, there is no correlation between CD marker profile and functional outcomes. Therefore, we aimed to discover novel predictive MSC chondrogenesis markers. The chondrogenic potential of primary human bone marrow MSCs (hBMSCs) over multiple passages was assessed by standard pellet culture. We confirmed that the ratio of TGFβ-RI/TGFβ-RII at the time of cell recovery from the tissue culture plastic reliably predicted chondrogenic potential. Furthermore, it is possible to prospectively characterize any human BMSC cell population as responders or non-responders with respect to chondrogenic differentiation potential. Transient increase of the ratio with siRNA knockdown of TGFβ-RII reproducibly recovered the chondrogenic differentiation ability of non-responsive MSCs. Together this offers an opportunity to produce a more functionally characterized cell population for use in autologous cartilage repair therapies.
KW - TGF receptor
KW - chondrogenic differentiation
KW - mesenchymal stem cell
KW - personalized medicine
KW - receptor ratio
UR - http://www.scopus.com/inward/record.url?scp=85087789072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087789072&partnerID=8YFLogxK
U2 - 10.3389/fbioe.2020.00618
DO - 10.3389/fbioe.2020.00618
M3 - Article
AN - SCOPUS:85087789072
SN - 2296-4185
VL - 8
JO - Frontiers in Bioengineering and Biotechnology
JF - Frontiers in Bioengineering and Biotechnology
M1 - 618
ER -