|
Angiogenesis [84]
|
IV
|
Human BM-MSCs; UCB-ECs
|
MSCs encouraged EC migration, proliferation, and tubule formation
|
GHK (osteonectin peptide) induces MSC-VEGF secretion
|
|
Angiogenesis [81]
|
IV
|
Human BM-MSCs (commercial); microvascular ECs
|
MSC culture on stiff, fibronectin-coated surfaces encouraged EC spreading/tubule formation
|
Actomyosin contractility increased MSC expression of proangiogenic factors (angiogenin, VEGF, and IGF)
|
|
Angiogenesis [105]
|
IV
|
Human BM-MSCs (commercial); UV-ECs
|
EC-MSC coculture increased MSC-myogenic and EC-PLAU, EC-FGF, and EC-NF-kB-regulated gene expression
|
• MSC IL-1β and IL-6 regulate EC NF-kB target genes, including P-selectin, CCL23, and CXCL2/3
|
|
• EC TGF-β1/3 may regulate MSC myogenic differentiation
|
|
Angiogenesis [107]
|
IV/mouse
|
Human BM-MSCs (commercial); UV-ECs
|
• IV: EC-MSC (vs EC) cultures on degradable scaffolds expressed higher perivascular markers
|
IV: cocultures upregulated VEGF and ANG1 while downregulating ANG2
|
|
• Host angiogenic and perivascular markers, except vessel diameter and density, were equivalent between EC/MSC-EC implants
|
|
Angiogenesis [73]
|
IV/mouse
|
Human iMSCs (medium change of iPSCs); UV-ECs
|
• iMSC exosomes promoted EC migration, proliferation, and dose-dependent tubule formation (IV)
|
iMSCs induced EC expression of proangiogenic molecules, including VEGF, TGF-β1, and ANG1
|
|
• Exosome treatment correlated with modest functional improvement, better perfusion and tissue damage scores, increased CD31/CD34+ cells
|
|
Angiogenesis (hindlimb ischemia) [22]
|
Mouse
|
Mouse AD-MSCs (plastic adherence); BM-MSCs (plastic adherence); BM-iMSCs (immunodepletion)
|
• BM-MSCs maximally decreased inflammatory cell invasion
|
IV: BM-MSCs expressed the highest levels of tested chemokines, vessel stabilizing, and matrix-remodeling factors
|
|
• MSCs were associated with smaller lesions, more mature neovascularization, and increased perfusion
|
|
Neurovascular system (fibrin conduit, resection) [116]
|
Rat
|
Human AD-MSCs (plastic adherence); DRG; UV-EC
|
• Medium cocktail-stimulated MSCs enhanced DRG neurite extension and EC-tubule formation
|
Stimulated MSCs produced increased VEGF, ANG1, NGF, BDNF, and GDNF
|
|
• Stimulated and unstimulated MSCs encouraged neurite extension
|
|
Neurogenesis [167]
|
IV
|
Rat BM-MSCs (plastic adherence)
|
Spinal cord tissue–MSC coculture supported neurite outgrowth
|
Cocultured MSCs produced NGF, BDNF, and GDNF, maximally supporting neurite extension
|
|
Neurogenesis (spinal nerve ligation) [123]
|
Rat
|
Rat BM-MSCs (commercial)
|
MSC-treated rats displayed decreased hyperalgesia and increased pain threshold
|
TUBB3–, GFAP–, and αSMA– and STRO1+ MSCs engrafted into DRGs
|
|
Neurogenesis (sciatic crush) [124]
|
Mouse
|
Human AD-MSCs and AM-MSCs (commercial)
|
• AM-MSC-treated groups exhibited higher recovery, coordination, and perfusion scores (4 weeks)
|
Nerves injected with AM-MSCs versus AD-MSCs or PBS produced more ANG1, FGF1, IGF1, and VEGFA
|
|
• MSCs localized in the epineurium and perivascular area
|
|
Distraction Osteogenesis (DO) [59]
|
Mouse
|
Human BM-MSCs (commercial)
|
• MSC and MSC-CM accelerated DO healing
|
• IV: IL-3/IL-6/CCL5/SDF1 recruited mononuclear cells, contributed to enhanced mineralization
|
|
• MSC-CM recruited more vessels
|
|
• MCP1/MCP3 but not SDF1 were critical for SC-CM osteogenic activity
|
|
Osteogenesis [168]
|
Mouse
|
Human AD-MSCs and BM-MSCs; UCB-ECs
|
• MSC-EC cotransplantation increased MSC engraftment
|
PDGFBB/PDGFRβ receptor activity regulates MSC engraftment and differentiation in the presence of ECs
|
|
• Cotransplantation restricted MSC multipotency, enhanced MSC source-related differentiation abilities, and maintained MSC proliferation capacity
|
|
Osteoporosis (lupus associated) [60]
|
Mouse
|
Human BM-MSCs and DP-MSCs
|
• MSC injections improved osteoporosis-related bone scores
|
IL-17 removal following MSC injection maintains osteoclast immaturity
|
|
• MSCs lowered osteoclast differentiation (IV)
|
|
Osteogenesis [169]
|
Rat
|
Rat BM-MSCs (centrifugation and plastic adherence)
|
Fibrin-loaded MSC recruited host macrophages to fill long bone defect by 4 weeks
|
Implanted MSCs increased early expression of VEGF and decreased later expression of CD45, IL-6, IL-1β, TNF-α, and IL-10
|
|
Osteogenesis, chondrogenesis, angiogenesis [170]
|
IV
|
Human BM-MSCs (density gradient) and human embryonic stem cell MSCs (medium/substrate changes); human aortic ECs
|
MSC-EC cocultures proliferated and exhibited higher expression of mesenchymal differentiation transcription factors
|
EC-produced ET1 activates MSC AKT, driving osteogenic and chondrogenic capacities
|
|
Chondrogenesis [95]
|
IV
|
Human BM-MSCs (density gradient)
|
• MSCs and/or chondrocytes in fibrin gels exhibited superior mechanical properties to those cultured with OA cartilage explants
|
IL-1β and IL-6 decreased COL production versus control cultures, except in chondrogenic cultures at longer culture times (4 weeks)
|
|
• COLI/II/III production reduced in OA cartilage–MSC or chondrocyte–MSC cocultures
|
|
Chondrogenesis [93]
|
IV
|
Human BM-MSCs; Human OA primary chondrocytes; bovine primary chondrocytes
|
FGF1 caused chondrocyte proliferation
|
• FGF1 was concentrated in places where MSCs contacted chondrocytes
|
|
Tenogenesis (enzymatic lesion) [152]
|
Horse
|
Horse AD-MSCs
|
Lesions were smaller, more vascularized, and less cellular when treated with platelet concentrate-injected MSCs
|
• Greater amount of RNA was recovered from the MSC-treated group
|
|
• No difference in anabolic and tendon-specific gene expression observed
|
|
Musculogenesis (dystrophin/utrophin) [135]
|
IV
|
Mouse quickly and slowly adhering MSCs (non-myogenic nmMSCs and MPCs), dKO)
|
• dKO-MPC-dKO-nmMSC co-culture decreased global myogenic markers
|
Soluble frizzled-related protein-1 and active β-catenin encouraged nonmyogenic differentiation of dKO-nmMSCs in gastrocnemius tissues
|
|
• dKO vs. WT-nmMSCs differentiated more efficiently along osteogenic and adipogenic lines with donor age
|
|
Musculogenesis (myofibroblast proliferation) [138]
|
IV
|
Human AD-MSCs and BM-MSCs (commercial); Dupuytren’s disease-derived myofibroblast (DDMF)
|
• AD-MSCs (similar to normal skin-derived fibroblasts) decreased while BM-MSCs increased DDMF co-culture contractility
|
AD-MSC/myofibroblast cocultures exhibited decreased COLI and αSMA
|
|
• AD-/BM-MSCs inhibited myofibroblast proliferation
|
|
• AD-MSC effects were strongest with direct or indirect contact
|
|
Musculogenesis (dystrophin) [160]
|
Mouse
|
Human (STRO1+) DP-MSCs; human (c-Kit+) amniotic fluid MSCs
|
• MSCs differentiated in the presence of C2C12-formed myotubes (IV)
|
Demethylation was critical for IV myogenic differentiation
|
|
• MSCs differentiated most efficiently with C2C12-CM
|
|
• All differentiated MSCs engrafted and improved muscle histology
|
|
Musculogenesis [137]
|
IV
|
Mouse BM-MSCs (centrifugation and plastic adherence)
|
MSC-CM stimulated myoblast and satellite cell proliferation and migration, activated satellite cells, inhibited myofibroblast differentiation
|
MSC MMP-2/9 and TIMP-1/2 support myogenic differentiation
|
