Table 2.
Preclinical methods for enhancing exogenous bone marrow stem and progenitor cell engraftment and function following injury.
| Molecules/methods | Cell type | Injured tissue | Ref. |
|---|---|---|---|
| Increased cell homing/engraftment | |||
| Enhancement of injured tissue homing/engraftment signal | |||
| SDF-1 local injection | EPC | Skeletal muscle | [148] |
| SDF-1 local gene therapy | EPC | Skeletal muscle | [149] |
| U/S to upregulate local SDF-1, VEGF, ICAM-1, VCAM-1 | MSC, BM-MNC | Heart | [198–201] |
| Low-energy shockwave to upregulate SDF-1 | EPC | Skeletal muscle | [150] |
| Systemic coadministration of growth factors/cytokines | |||
| G-CSF | BM-MNC | Brain, liver | [202,203] |
| HGF | BM-MNC | Liver | [204] |
| SDF-1 | BM-MNC | Liver | [205] |
| Ex vivo modulation of cell function: gene therapies | |||
| Enhancement of cell homing/function | |||
| eNOS, CXCR4 | MSC, EPC | Artery, heart | [157,158,166–169,206] |
| Enhancement of cell survival | |||
| TERT | EPC | Skeletal muscle | [207] |
| HSP-70, Bcl-2, Akt, GSK, ILK | MSC | Heart | [152–156] |
| Enhancement of cell survival/paracrine signaling | |||
| HGF | EPC | Artery | [164] |
| VEGF | EPC | Skeletal muscle | [163] |
| SDF-1 | MSC | Heart | [165] |
| IGF-1 | EPC | Heart | [208] |
| Ex vivo modulation of cell function: small molecules | |||
| Enhancement of cell survival/function | |||
| AVE9488 (eNOS enhancer) | EPC | Heart | [159] |
| PPARγ agonist | MSC | Heart | [209] |
| Inhibition of apoptosis | |||
| p38 kinase inhibitor | EPC | Skeletal muscle | [210] |
| Activation of selectins/integrins | |||
| Ephrin-B2-Fc, activating β2-integrin antibody | EPC | Skeletal muscle | [170,171] |
| Enhancement of paracrine signaling | |||
| TGF-α, estradiol | MSC | Heart | [172,173] |
| Enhancement of differentiation capacity | |||
| Angiotensin receptor blocker | MSC | Heart | [211] |
| Altered cellular microenvironment | |||
| Bioscaffolds | MSC | Heart, skin, bone | [180–184,187–189] |
| Combined approaches | |||
| Ex vivo VEGF gene therapy with local SDF-1 delivery | EPC | Heart | [174] |
| Bioscaffold with SDF-1 pretreatment | EPC | Heart | [212] |
| Bioscaffold with IL-10 gene therapy | MSC | Heart | [213] |
BM-MNC: Bone marrow-derived mononuclear cell; EPC: Endothelial progenitor cell; Ephrin-B2-Fc: Ligand for erythropoietin-producing human hepatocellular carcinoma receptor B4; MSC: Mesenchymal stem cell; U/S: Ultrasound.