Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration
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 u...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2021/4465022 |
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| author | Lingling E Rongjian Lu Jianwei Sun Hongbo Li Wen Xu Helin Xing Xing Wang Tao Cheng Shuo Zhang Xiaocao Ma Rong Zhang Hongchen Liu |
| author_facet | Lingling E Rongjian Lu Jianwei Sun Hongbo Li Wen Xu Helin Xing Xing Wang Tao Cheng Shuo Zhang Xiaocao Ma Rong Zhang Hongchen Liu |
| author_sort | Lingling E |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f64789754e8b4281a24abe035158882d |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-f64789754e8b4281a24abe035158882d2025-02-03T01:12:53ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/44650224465022Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone RegenerationLingling E0Rongjian Lu1Jianwei Sun2Hongbo Li3Wen Xu4Helin Xing5Xing Wang6Tao Cheng7Shuo Zhang8Xiaocao Ma9Rong Zhang10Hongchen Liu11Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Stomatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, ChinaGuangzhou Special Service Recuperation Center of PLA Rocket Force, Guangzhou, 510010 Guangdong Province, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaThe 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.http://dx.doi.org/10.1155/2021/4465022 |
| spellingShingle | Lingling E Rongjian Lu Jianwei Sun Hongbo Li Wen Xu Helin Xing Xing Wang Tao Cheng Shuo Zhang Xiaocao Ma Rong Zhang Hongchen Liu Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration Stem Cells International |
| title | Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration |
| title_full | Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration |
| title_fullStr | Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration |
| title_full_unstemmed | Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration |
| title_short | Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration |
| title_sort | microenvironment influences on human umbilical cord mesenchymal stem cell based bone regeneration |
| url | http://dx.doi.org/10.1155/2021/4465022 |
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