PMID- 36906634 OWN - NLM STAT- MEDLINE DCOM- 20230314 LR - 20230314 IS - 1749-799X (Electronic) IS - 1749-799X (Linking) VI - 18 IP - 1 DP - 2023 Mar 11 TI - Bone marrow-derived dedifferentiated fat cells exhibit similar phenotype as bone marrow mesenchymal stem cells with high osteogenic differentiation and bone regeneration ability. PG - 191 LID - 10.1186/s13018-023-03678-9 [doi] LID - 191 AB - BACKGROUND: Mesenchymal stem cells (MSCs) are known to have different differentiation potential depending on the tissue of origin. Dedifferentiated fat cells (DFATs) are MSC-like multipotent cells that can be prepared from mature adipocytes by ceiling culture method. It is still unknown whether DFATs derived from adipocytes in different tissue showed different phenotype and functional properties. In the present study, we prepared bone marrow (BM)-derived DFATs (BM-DFATs), BM-MSCs, subcutaneous (SC) adipose tissue-derived DFATs (SC-DFATs), and adipose tissue-derived stem cells (ASCs) from donor-matched tissue samples. Then, we compared their phenotypes and multilineage differentiation potential in vitro. We also evaluated in vivo bone regeneration ability of these cells using a mouse femoral fracture model. METHODS: BM-DFATs, SC-DFATs, BM-MSCs, and ASCs were prepared from tissue samples of knee osteoarthritis patients who received total knee arthroplasty. Cell surface antigens, gene expression profile, and in vitro differentiation capacity of these cells were determined. In vivo bone regenerative ability of these cells was evaluated by micro-computed tomography imaging at 28 days after local injection of the cells with peptide hydrogel (PHG) in the femoral fracture model in severe combined immunodeficiency mice. RESULTS: BM-DFATs were successfully generated at similar efficiency as SC-DFATs. Cell surface antigen and gene expression profiles of BM-DFATs were similar to those of BM-MSCs, whereas these profiles of SC-DFATs were similar to those of ASCs. In vitro differentiation analysis revealed that BM-DFATs and BM-MSCs had higher differentiation tendency toward osteoblasts and lower differentiation tendency toward adipocytes compared to SC-DFATs and ASCs. Transplantation of BM-DFATs and BM-MSCs with PHG enhanced bone mineral density at the injection sites compared to PHG alone in the mouse femoral fracture model. CONCLUSIONS: We showed that phenotypic characteristics of BM-DFATs were similar to those of BM-MSCs. BM-DFATs exhibited higher osteogenic differentiation potential and bone regenerative ability compared to SC-DFATs and ASCs. These results suggest that BM-DFATs may be suitable sources of cell-based therapies for patients with nonunion bone fracture. CI - (c) 2023. The Author(s). FAU - Sawada, Hirokatsu AU - Sawada H AD - Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan. FAU - Kazama, Tomohiko AU - Kazama T AD - Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-Ku, Tokyo, 173-8610, Japan. FAU - Nagaoka, Yuki AU - Nagaoka Y AD - Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-Ku, Tokyo, 173-8610, Japan. FAU - Arai, Yoshinori AU - Arai Y AD - Department of Oral and Maxillofacial Radiology, Nihon University School of Dentistry, Tokyo, Japan. FAU - Kano, Koichiro AU - Kano K AD - Laboratory of Cell and Tissue Biology, College of Bioresource Sciences, Nihon University, Fujisawa, Japan. FAU - Uei, Hiroshi AU - Uei H AD - Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan. FAU - Tokuhashi, Yasuaki AU - Tokuhashi Y AD - Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan. FAU - Nakanishi, Kazuyoshi AU - Nakanishi K AD - Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan. FAU - Matsumoto, Taro AU - Matsumoto T AD - Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-Ku, Tokyo, 173-8610, Japan. matsumoto.taro@nihon-u.ac.jp. LA - eng GR - 20H03581/Japan Society for the Promotion of Science/ GR - 21bk010412h001/Japan Agency for Medical Research and Development/ GR - 2021-2022/The Research Grant from the Chairperson and the President of Nihon University/ PT - Journal Article DEP - 20230311 PL - England TA - J Orthop Surg Res JT - Journal of orthopaedic surgery and research JID - 101265112 SB - IM MH - Humans MH - Osteogenesis MH - Bone Marrow MH - X-Ray Microtomography MH - Adipose Tissue MH - Adipocytes MH - *Mesenchymal Stem Cells/metabolism MH - Cell Differentiation MH - Bone Regeneration MH - Cells, Cultured MH - Phenotype MH - Bone Marrow Cells/metabolism MH - *Femoral Fractures/metabolism PMC - PMC10007822 OTO - NOTNLM OT - Adipocytes OT - Cell therapy OT - Dedifferentiated fat cells OT - Mesenchymal stem cells OT - Nonunion bone fracture COIS- The authors declare that they have no competing interests. EDAT- 2023/03/13 06:00 MHDA- 2023/03/15 06:00 PMCR- 2023/03/11 CRDT- 2023/03/11 23:19 PHST- 2022/03/10 00:00 [received] PHST- 2023/03/04 00:00 [accepted] PHST- 2023/03/11 23:19 [entrez] PHST- 2023/03/13 06:00 [pubmed] PHST- 2023/03/15 06:00 [medline] PHST- 2023/03/11 00:00 [pmc-release] AID - 10.1186/s13018-023-03678-9 [pii] AID - 3678 [pii] AID - 10.1186/s13018-023-03678-9 [doi] PST - epublish SO - J Orthop Surg Res. 2023 Mar 11;18(1):191. doi: 10.1186/s13018-023-03678-9.