Mesenchymal Stem Cell Migration and Tissue Repair
Abstract
:1. Introduction
2. Chemical Factors Regulating BMSC Migration
2.1. SDF-1/CXCR4 Axis
2.2. Osteopontin (OPN)
2.3. Growth Factors
2.3.1. bFGF
2.3.2. VEGF
2.3.3. HGF
2.3.4. IGF-1
2.3.5. PDGF
2.3.6. TGF-β1
3. Mechanical Factors Regulating BMSC Migration
3.1. Mechanical Strain
3.2. Shear Stress
3.3. Matrix Stiffness
3.4. Microgravity
Mechanical Regime | Cell Migration | Outcomes | References |
---|---|---|---|
Mechanical stretch (5%, 6 h) | ↑ | Enhanced homing and transdifferentiation of BMSCs under mechanical stretch in the expanded skin, and BMSCs were recruited to sites where SDF-1αwas most highly expressed. | [67] |
Mechanical stretch (10%, 8 h) | ↑ | Promoted BMSC migration via FAK and ERK1/2 signals. | [68] |
Mechanical stretch (10%, 12 h) | ↑ | In vivo and in vitro results showed that mechanical stretch can upregulate SDF-1α in skin and recruit circulating BMSCs through the SDF-1α/CXCR4 pathway. | [70] |
Shear stress (0.2 Pa/>2 Pa) | ↓↑ | High shear stress (>2 Pa) hindered human BMSC migration, whereas lower shear stress (0.2 Pa) induced cell migration. | [71] |
Shear stress (0.2 Pa) | ↑ | The SDF-1/CXCR4 axis mediated low-shear-stress-induced human BMSC migration through the JNK and p38 MAPK pathways. | [72] |
Matrix stiffness (1 kPa, 2.3 h; 34 kPa, 6.3 h) | ↑ | BMSCs migrated from the soft matrix to the stiff matrix by polarizing the cytoskeleton function and the phosphorylated myosin-II heavy chain. | [74] |
Matrix stiffness (≥5-6 kPa, 2 h) | ↑ | Extracellular matrix (ECM) stiffness influenced the position of the microtubule organizing center (MTOC) in MSCs by polarizing it in front of the nucleus only when the matrix was sufficiently stiff, which increased MSC migration. | [75] |
Matrix stiffness (1 to 12 kPa, 3 days) | ↑ | Human MSCs migrated to stiffer portions of the substrates by increasing the assembled microtubule network. | [73] |
Matrix stiffness (2 kPa, 4 h) | ↑ | AFSCs cultured on softer substrates secreted more autocrine cytokines, which increased AFSC migration. | [76] |
Microgravity (rotated at 10 rpm, approximately 1 × 10−3 g; 24 h) | ↓ | The migration of BMSCs was inhibited by simulated microgravity via reorganizing F-actin and increasing cell stiffness. | [82] |
Microgravity (rotated at 10 to 12 rpm, approximately 1 × 10–3 g to 1.2×10–3 g; 2 to 3 days) | ↓ | The culture of HSCs in a microgravity environment inhibited the migration of HSCs by a significant reduction of SDF-1α-directed migration, which correlated with a decreased expression of F-actin. | [83] |
4. Mechanisms of BMSCs in Tissue Repair
4.1. BMSC Paracrine Factors and Tissue Repair
4.1.1. Paracrine Factors of Transplanting BMSCs
4.1.2. Conditioned Medium from BMSCs for Tissue Repair
4.2. Directed Differentiation of BMSCs and Tissue Repair
5. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AFSCs | Amniotic fluid-derived stem cells |
bFGF | Basic fibroblast growth factor |
BMSCs | Bone marrow-derived mesenchymal stem cells |
BMSC-CM | Conditioned medium from BMSCs |
CCL2 | CC chemokine ligand 2 |
CCR2 | CC chemokine receptor 2 |
CM | Conditioned medium |
CRE | Cockroach allergen extract |
CXCL7 | Chemokine (C-X-C motif) ligand 7 |
CXCR4 | CXC chemokine receptor 4 |
ECM | Extracellular matrix |
EGF | Epithelial growth factor |
ERK1/2 | Extracellular signal-regulated kinase 1/2 |
ESCs | Embryonic stem cells |
FAK | Focal adhesion kinase |
Flt3 | Fms-like tyrosine kinase 3 |
GDF-11 | Growth differentiation factor-11 |
GFP | Green fluorescent protein |
HGF | Hepatocyte growth factor |
HSCs | Hematopoietic stem cells |
HMGB1 | High mobility group box 1 |
IGF-1 | Insulin-like growth factor-1 |
IL1-RA | Interleukin-1 receptor antagonist |
IL-6 | Interleukin 6 |
IL-8 | Interleukin-8 |
IL-10 | Interleukin-10 |
JNK | c-Jun N-terminal kinase |
LL-37 | Leu-Leu-37 |
MAPK | Mitogen-activated protein kinase |
MCP-1 | Monocyte chemoattractant protein-1 |
MSCs | Mesenchymal stem cells |
MTOC | Microtubule organizing center |
NF-κB | Nuclear factor kappa B |
NGF | Nerve growth factor |
NOD/SCID | Non-obese diabetic/severe combined immunodeficiency |
OPN | Osteopontin |
PDGF | Platelet derived growth factor |
PDGF-AB | Platelet derived growth factor isoforms AB |
PDGF-BB | Platelet derived growth factor isoforms BB |
PDGF-CC | Platelet derived growth factor isoforms CC |
PDGFRs | Platelet-derived growth factor receptors |
PDGFR-α | Platelet-derived growth factor receptor isoform α |
PDGFR-β | Platelet-derived growth factor receptor isoform β |
PI3K | Phosphatidylinositol 3-kinase |
RAGE | Receptor for advanced glycation end |
Rho A | Ras homolog gene family member A |
SCF | Stem cell factor |
SDF-1 | Stromal derived factor-1 |
SUN1 | Sad-1/UNC-84 1 |
TGF-β1 | Transforming growth factor β1 |
TNF-α | Tumor necrosis factor |
UC-MSC-CM | Umbilical cord blood-derived mesenchymal stem cells conditioned media |
VEGF | Vascular endothelial growth factor |
VEGFR | Vascular endothelial growth factor receptor |
WJ-MSCs | Wharton’s jelly-derived mesenchymal stem cells |
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Chemical Factor | Concentration | Cell Migration | Outcomes | References |
---|---|---|---|---|
Stromal derived factor-1(SDF-1) | 50 ng/mL, 100 ng/mL | ↑ | SDF-1 increased BMSC recruitment to injured liver and promoted the repair of injured liver. | [16] |
SDF-1 | 100 ng/mL | ↑ | SDF-1 increased BMSCs with CXCR4 expression and promoted the repair of traumatic brain injury. | [17] |
SDF-1 | 10 ng/mL | ↑ | SDF-1 increased stem cell recruitment, and the pretreatment of stem cells (Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), embryonic stem cells (ESCs)) enhanced skeletal muscle regeneration. | [18] |
Osteopontin (OPN) | 1 μg/mL | ↑ | Increased integrin β1 expression in BMSCs and promoted BMSC migration through the ligation to integrin β1. | [19] |
OPN | 10 μg/mL, 20 μg/mL | ↑ | Increased mesenchymal stem cell (MSC) migration in a dose-dependent manner. | [20] |
OPN | 1 μg/mL | ↑ | OPN reduced the number of organized actin cytoskeletons through the FAK and ERK pathways to increase BMSC migration. | [21] |
OPN | 1 μg/mL | ↑ | Reduced the number of organized actin cytoskeletons through the FAK and ERK pathways to increase BMSC migration. | [22] |
OPN | 1 μg/mL | ↑ | Cytoskeletal control of nuclear morphology and stiffness through the SUN1 proteins plays an important role in OPN-promoted BMSC migration. | [23] |
OPN | 1 μg/mL | ↑ | Chromatin organization was altered by the application of OPN via the ERK1/2 signaling pathway, which also contributed to BMSC migration. | [24] |
Basic fibroblast growth factor (bFGF) | 200 ng/mL | ↑ | Augmented the engraftment and differentiation capacity of transplanted BMSCs, recovering cardiac function. | [25] |
bFGF | 1 ng/mL up to 400 ng/mL | ↓↑ | Low concentrations led to an attraction of BMSCs, whereas higher concentrations resulted in repulsion. | [26] |
Vascular endothelial growth factor (VEGF)-A | 10 ng/mL | ↑ | Increased BMSC migration and proliferation. | [27] |
Hepatocyte growth factor (HGF) | 20 ng/mL | ↑ | Increased BMSC migration via PI3K pathways. | [28] |
Insulin-like growth factor (IGF)-1 | 10 ng/mL | ↑ | Increased BMSC migratory responses via CXCR4 chemokine receptor signaling, which is PI3/Akt-dependent. | [29] |
IGF-1 | 20 ng/mL | ↑ | Preconditioning of BMSCs with IGF-1 before infusion improved cell migration capacity and restored normal renal function after acute kidney injury. | [30] |
Platelet-derived growth factor (PDGF) | 50 ng/mL | ↑ | Increased BMSC migration significantly. | [31] |
PDGF-B | 40 ng/mL | ↑ | Increased recruitment/migration and differentiation of BMSCs. | [32] |
Transforming growth factor (TGF)-β 1 | 100 pM | ↑ | Promoted the homing of BMSCs in myocardial ischemia/reperfusion injury and improved myocardial function. | [9] |
TGF-β1 | 5 ng/mL | ↑ | Improved BMSC recruitment and wound closure in a syngeneic murine wound model. | [33] |
TGF-β | 1 ng/mL~100 ng/mL | ↑ | Activated noncanonical signaling molecules, such as Akt, ERK1/2, FAK, and p38, via TGF-β type I receptor to increase stem cell (BMSCs, BM-MSC-like ST2 cells) migration. | [34] |
Paracrine Factors | Animal Models | Outcomes | References |
---|---|---|---|
TGF-β, FGF-2, angiopoietin-2, VEGF-1 | Rat myocardial infarction model | Triggered angiogenic and migratory effects at the site of the infarct to promote myocardial healing and improve the cardiac function. | [1] |
NGF, HGF, IL-10, IL1-RA | NOD/SCID mouse model | Contributed to the prevention of apoptosis, increasing cell proliferation in the damaged liver. | [86] |
TGF-β1, VEGF | Mouse burn injury model | Assisted in burn wound healing. | [2] |
IGF-1 | Mouse acute kidney injury model | Exerted beneficial effects on tubular cell repair in acute kidney injury. | [87] |
Angiogenin, IL-8, MCP-1, and VEGF | Mouse hind limb ischemia model | Represented efficient biomarkers for predicting vascular regenerative efficacy of MSCs. | [4] |
IGF-1, VEGF, EGF, and bFGF | Rat middle cerebral artery occlusion ischemia model | Induced functional improvement, reduced infarct volume, and showed neuroprotection in ischemic rats. | [88] |
TGF-β | Rat stroke model | Suppressed immune propagation in the ischemic rat brain. | [89] |
SDF-1, VEGF, HGF, and IL-6 | Rat skin wound model | Enhanced the activity of dermal fibroblasts and keratinocytes to promote re-epithelialization and angiogenesis and, consequently, promoted wound healing. | [5] |
Conditioned Medium | Animal Models | Outcomes | References |
---|---|---|---|
IGF-1, VEGF, TGF-β1 and HGF | Rat periodontal defect model | Contributed to many processes of complicated periodontal tissue regeneration. | [3] |
IL-6, IL-8 | Rat hind limb ischemia model | Stimulated angiogenesis and tissue repair through an increase in homing of human cord blood-derived endothelial progenitor. | [90] |
EGF, bFGF, PDGF, HGF, collagen type 1, and GDF-11 | In vivo human test | Stimulated skin rejuvenation by increasing growth and ECM production. | [91] |
Collagen types III and I and a high MMPs/TIMPs ratio | Mouse skin excisional wound model | Accelerated healing, with fewer scars compared with control groups. | [92] |
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Fu, X.; Liu, G.; Halim, A.; Ju, Y.; Luo, Q.; Song, G. Mesenchymal Stem Cell Migration and Tissue Repair. Cells 2019, 8, 784. https://doi.org/10.3390/cells8080784
Fu X, Liu G, Halim A, Ju Y, Luo Q, Song G. Mesenchymal Stem Cell Migration and Tissue Repair. Cells. 2019; 8(8):784. https://doi.org/10.3390/cells8080784
Chicago/Turabian StyleFu, Xiaorong, Ge Liu, Alexander Halim, Yang Ju, Qing Luo, and Guanbin Song. 2019. "Mesenchymal Stem Cell Migration and Tissue Repair" Cells 8, no. 8: 784. https://doi.org/10.3390/cells8080784