Identification of a clinical signature predictive of differentiation fate of human bone marrow stromal cells
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Identification of a clinical signature predictive of differentiation fate of human bone marrow stromal cells. / Kowal, Justyna Magdalena; Möller, Sören; Ali, Dalia; Figeac, Florence; Barington, Torben; Schmal, Hagen; Kassem, Moustapha.
I: Stem Cell Research and Therapy, Bind 12, 265, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of a clinical signature predictive of differentiation fate of human bone marrow stromal cells
AU - Kowal, Justyna Magdalena
AU - Möller, Sören
AU - Ali, Dalia
AU - Figeac, Florence
AU - Barington, Torben
AU - Schmal, Hagen
AU - Kassem, Moustapha
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021
Y1 - 2021
N2 - Background: Transplantation of human bone marrow stromal cells (hBMSCs) is a promising therapy for bone regeneration due to their ability to differentiate into bone forming osteoblastic cells. However, transplanted hBMSCs exhibit variable capacity for bone formation resulting in inconsistent clinical outcome. The aim of the study was to identify a set of donor- and cell-related characteristics that detect hBMSCs with optimal osteoblastic differentiation capacity. Methods: We collected hBMSCs from 58 patients undergoing surgery for bone fracture. Clinical profile of the donors and in vitro characteristics of cultured hBMSCs were included in uni- and multivariable analysis to determine their predictive value for osteoblastic versus adipocytic differentiation capacity assessed by quantification of mineralized matrix and mature adipocyte formation, respectively. Results: We identified a signature that explained > 50% of variation in osteoblastic differentiation outcome which included the following positive predictors: donor sex (male), absence of osteoporosis diagnosis, intake of vitamin D supplements, higher fraction of CD146+, and alkaline phosphate (ALP+) cells. With the exception of vitamin D and ALP+ cells, these variables were also negative predictors of adipocytic differentiation. Conclusions: Using a combination of clinical and cellular criteria, it is possible to predict differentiation outcome of hBMSCs. This signature may be helpful in selecting donor cells in clinical trials of bone regeneration.
AB - Background: Transplantation of human bone marrow stromal cells (hBMSCs) is a promising therapy for bone regeneration due to their ability to differentiate into bone forming osteoblastic cells. However, transplanted hBMSCs exhibit variable capacity for bone formation resulting in inconsistent clinical outcome. The aim of the study was to identify a set of donor- and cell-related characteristics that detect hBMSCs with optimal osteoblastic differentiation capacity. Methods: We collected hBMSCs from 58 patients undergoing surgery for bone fracture. Clinical profile of the donors and in vitro characteristics of cultured hBMSCs were included in uni- and multivariable analysis to determine their predictive value for osteoblastic versus adipocytic differentiation capacity assessed by quantification of mineralized matrix and mature adipocyte formation, respectively. Results: We identified a signature that explained > 50% of variation in osteoblastic differentiation outcome which included the following positive predictors: donor sex (male), absence of osteoporosis diagnosis, intake of vitamin D supplements, higher fraction of CD146+, and alkaline phosphate (ALP+) cells. With the exception of vitamin D and ALP+ cells, these variables were also negative predictors of adipocytic differentiation. Conclusions: Using a combination of clinical and cellular criteria, it is possible to predict differentiation outcome of hBMSCs. This signature may be helpful in selecting donor cells in clinical trials of bone regeneration.
KW - CD markers
KW - Cell phenotype
KW - Donor characteristics
KW - Human bone marrow stromal stem cells
KW - Osteoblastic and adipocytic differentiation
U2 - 10.1186/s13287-021-02338-1
DO - 10.1186/s13287-021-02338-1
M3 - Journal article
C2 - 33941262
AN - SCOPUS:85105119033
VL - 12
JO - Stem Cell Research & Therapy
JF - Stem Cell Research & Therapy
SN - 1757-6512
M1 - 265
ER -
ID: 262795458