Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment
Abstract
:1. Introduction
2. Mesenchymal Stem Cells (MSCs) and Bone Marrow MSCs (BM-MSCs) in Osteoporosis Development
3. The Molecular Mechanisms Regulating Osteoblast and Adipocyte Differentiation of MSCs
3.1. Transcription Factors
3.2. Signaling Pathways
3.3. MicroRNAs
3.4. Other Factors
4. Therapeutic Applications of MSCs for Osteoporosis
4.1. Bone Marrow MSCs (BM-MSCs)
4.2. Adipose Tissue-Derived MSCs (AD-MSCs)
5. Concerns on the Clinical Application of MSCs in Osteoporosis Treatment and Future Direction
6. Conclusions and Perspectives
Acknowledgments
Conflicts of Interest
Abbreviations
AD-MSCs | adipose tissue-derived MSCs |
ADSC | adipose tissue-derived stromal cell |
ALP | alkaline phosphatase |
bFGF | basic fibroblast growth factor |
BMD | bone mineral density |
BM-MSCs | bone marrow MSCs |
BMP | bone morphogenic protein |
BMPR | bone morphogenetic protein receptor |
Cbfa1 | core binding factor α1 |
Cbfβ | core binding factor β |
C/EBPα | CCAAT/enhancer binding protein α |
CXCR4 | C-X-C chemokine receptor type 4 |
Dlx5 | distal-less homeobox 5 |
ERK1/2 | extracellular signal-regulated kinase 1/2 |
Foxa1 | forkhead transcription factor 1 |
Foxc2 | forkhead box C2 |
Frz | frizzled |
GMP | good manufacturing practices |
GSK3β | glycogen synthase kinase 3 β |
HGF | hepatocyte growth factor |
HLA-DR | human leukocyte antigen-antigen D related |
HOXC8 | homeobox C8 |
hTERT | human telomerase reverse transcriptase |
LMHF | low magnitude high frequency |
LRP5/6 | low-density lipoprotein receptor-related protein 5/6 |
MAPK | mitogen-activated protein kinase |
miRNA | microRNA |
MSCs | mesenchymal stem cells |
OC | osteocalcin |
OVX | ovariectomy |
PDGF-BB | platelet derived growth factor B |
PI3K | phosphoinositide 3-kinase |
PPARγ | peroxisome proliferation-activated receptor γ |
PTH | parathyroid hormone |
RANKL | receptor activator of nuclear factor-kappa B ligand |
Runx2 | runt-related transcription factor 2 |
SAMP6 | senescence accelerated mouse prone 6 |
SDF-1 | stromal-derived factor-1 |
TAK1 | transforming growth factor-β activated kinase 1 |
TGF-β | transforming growth factor-β |
Wnt | wingless and int-1 |
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Cell Type | Treatment Method | Therapeutic Outcomes | References |
---|---|---|---|
BM-MSCs | Local transplantation of autologous BM-MSCs | Increased trabecular thickness, improved microstructures with newly formed osteoids, and enhanced trabecular thickness and stiffness of bone. | [125] |
BM-MSCs | Local injection of the normal allogeneic BM-MSCs | Increased trabecular bone, attenuated the loss of BMD, improved the femur bone mass and prevented osteoporosis. | [126,127] |
BM-MSCs | Systemic injection of allogeneic BM-MSCs | Promoted osteoblastogenesis, maintained bone formation, and prevented the reduction of bone mass and strength in osteoporotic mouse model. Increased bone formation and sustained microarchitectural competence in a mouse model of age-related osteoporosis. | [128,129] |
AD-MSCs | Systemic injection of allogeneic AD-MSCs | Prevented OVX-induced bone loss. | [132] |
AD-MSCs | Local injection of autologous AD-MSCs | Improved trabecular bone quality and induced a significant increase in several molecular markers of bone turnover. Promoted osteogenesis, inhibited adipogenesis, and increased bone mineral density and new bone formation. | [133,134] |
Cell Type | Treatment Method | Disease Treated | No. of Patients | Dose (No. of Treatment) | Phase | Therapeutic Outcomes | Clinical Trial No. |
---|---|---|---|---|---|---|---|
BM-MSCs | Intravenous injection of autologous BM-MSCs that were fucosylated | Osteoporosis, Spinal fractures | 10 | First 4 patients receive 2 million cells/kg; last 6 receive 5 million cells/kg (Single) | Phase I | Still in progress, no results | NCT02566655 |
AD-MSCs | AD-MSCs were seeded within a composite graft and transplanted back into the fracture site | Osteoporotic fractures | 8 | Unknown | Phase II | Terminated, no results | NCT01532076 |
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Hu, L.; Yin, C.; Zhao, F.; Ali, A.; Ma, J.; Qian, A. Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment. Int. J. Mol. Sci. 2018, 19, 360. https://doi.org/10.3390/ijms19020360
Hu L, Yin C, Zhao F, Ali A, Ma J, Qian A. Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment. International Journal of Molecular Sciences. 2018; 19(2):360. https://doi.org/10.3390/ijms19020360
Chicago/Turabian StyleHu, Lifang, Chong Yin, Fan Zhao, Arshad Ali, Jianhua Ma, and Airong Qian. 2018. "Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment" International Journal of Molecular Sciences 19, no. 2: 360. https://doi.org/10.3390/ijms19020360