PMID- 34447439 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210828 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2021 DP - 2021 TI - Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration. PG - 4465022 LID - 10.1155/2021/4465022 [doi] LID - 4465022 AB - The microenvironment, or niche, regulates stem cell fate and improves differentiation efficiency. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are ideal cell source for bone tissue engineering. However, the role of the microenvironments in hUC-MSC-based bone regeneration is not yet fully understood. This study is aimed at investigating the effects of the in vitro culture microenvironment (hUC-MSCs, nano-hydroxyapatite/collagen/poly (L-lactide) (nHAC/PLA), osteogenic media (OMD), and recombinant human bone morphogenetic protein-7 (rhBMP-7)) and the in vivo transplanted microenvironment (ectopic and orthotopic) on bone regeneration ability of hUC-MSCs. The isolated hUC-MSCs showed self-renewal potential and MSCs' characteristics. In the in vitro two-dimensional culture microenvironment, OMD or OMD with rhBMP-7 significantly enhanced hUC-MSCs' osteocalcin immunofluorescence staining, alkaline phosphatase, and Alizarin red staining; OMD with rhBMP-7 exhibited the highest ALP secretion and mineralized matrix formation. In the in vitro three-dimensional culture microenvironment, nHAC/PLA supported hUC-MSCs' adhesion, proliferation, and differentiation; the microenvironment containing OMD or OMD and rhBMP-7 shortened cell proliferation progression and made osteogenic differentiation progression advance; rhBMP-7 significantly attenuated the inhibiting effect of OMD on hUC-MSCs' proliferation and significantly enhanced the promoting effect of OMD on gene expression and protein secretion of osteogenic differentiation markers, calcium and phosphorous concentration, and mineralized matrix formation. The in vitro three-dimensional culture microenvironment containing OMD and rhBMP-7 induced hUC-MSCs to form the most new bones in ectopic or orthotopic microenvironment as proved by microcomputed tomography and hematoxylin and eosin staining, but bone formation in orthotopic microenvironment was significantly higher than that in ectopic microenvironment. The results indicated that the combination of in vitro hUC-MSCs+nHAC/PLA+OMD+rhBMP-7 microenvironment and in vivo orthotopic microenvironment provided a more optimized niche for bone regeneration of hUC-MSCs. This study elucidates that hUC-MSCs and their local microenvironment, or niche, play an important role in hUC-MSC-based bone regeneration. The endogenously produced BMP may serve an important regulatory role in the process. CI - Copyright (c) 2021 Lingling E et al. FAU - E, Lingling AU - E L AUID- ORCID: 0000-0003-1955-9851 AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Lu, Rongjian AU - Lu R AD - Department of Stomatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China. FAU - Sun, Jianwei AU - Sun J AD - Guangzhou Special Service Recuperation Center of PLA Rocket Force, Guangzhou, 510010 Guangdong Province, China. FAU - Li, Hongbo AU - Li H AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Xu, Wen AU - Xu W AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Xing, Helin AU - Xing H AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Wang, Xing AU - Wang X AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Cheng, Tao AU - Cheng T AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Zhang, Shuo AU - Zhang S AUID- ORCID: 0000-0002-6526-5777 AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Ma, Xiaocao AU - Ma X AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. FAU - Zhang, Rong AU - Zhang R AUID- ORCID: 0000-0002-4768-8311 AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. AD - Institute for the Prevention and Control of Major Health and Public Safety Events of Armed Police, No. 9 Fuan Street, Beijing 102600, China. FAU - Liu, Hongchen AU - Liu H AUID- ORCID: 0000-0003-2406-5346 AD - Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. LA - eng PT - Journal Article DEP - 20210817 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC8384552 COIS- The authors declare that there are no conflicts of interest. EDAT- 2021/08/28 06:00 MHDA- 2021/08/28 06:01 PMCR- 2021/08/17 CRDT- 2021/08/27 06:54 PHST- 2021/05/25 00:00 [received] PHST- 2021/07/26 00:00 [accepted] PHST- 2021/08/27 06:54 [entrez] PHST- 2021/08/28 06:00 [pubmed] PHST- 2021/08/28 06:01 [medline] PHST- 2021/08/17 00:00 [pmc-release] AID - 10.1155/2021/4465022 [doi] PST - epublish SO - Stem Cells Int. 2021 Aug 17;2021:4465022. doi: 10.1155/2021/4465022. eCollection 2021.