Justyna Magdalena Kowal1,2, Sören Möller3, Dalia Ali4,5, Florence Figeac4,5, Torben Barington6,7, Hagen Schmal8,9, Moustapha Kassem4,5,10. 1. Department of Endocrinology, Odense University Hospital, Odense, Denmark. jkowal@health.sdu.dk. 2. Molecular Endocrinology Unit (KMEB), Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. jkowal@health.sdu.dk. 3. OPEN - Open Patient data Explorative Network, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark. 4. Department of Endocrinology, Odense University Hospital, Odense, Denmark. 5. Molecular Endocrinology Unit (KMEB), Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. 6. Department of Clinical Immunology, Odense University Hospital, Odense, Denmark. 7. Department of Clinical Research, University of Southern Denmark, Odense, Denmark. 8. Department of Orthopedics and Traumatology, Odense University Hospital, Odense, Denmark. 9. Department of Orthopedics and Trauma Surgery, Medical Center - Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany. 10. Department of Cellular and Molecular Medicine, Danish Stem Cell Center (DanStem), University of Copenhagen, 2200, Copenhagen, Denmark.
Abstract
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.
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.
Entities:
Keywords:
CD markers; Cell phenotype; Donor characteristics; Human bone marrow stromal stem cells; Osteoblastic and adipocytic differentiation
Authors: Alexander N Comninos; Morten S Hansen; Alan Courtney; Sirazum Choudhury; Lisa Yang; Edouard G Mills; Maria Phylactou; Mark Busbridge; Muaza Khir; Thilipan Thaventhiran; Paul Bech; Tricia Tan; Ali Abbara; Morten Frost; Waljit S Dhillo Journal: J Clin Endocrinol Metab Date: 2022-05-17 Impact factor: 6.134