Table 2.
Influence of genetic manipulation on heterogeneity of MSC
| Genetic modification | MSC source | Type of study | Effect on MSC/therapeutic benefits | References |
|---|---|---|---|---|
|
Sox2 Oct4 transduction |
hAD-MSC | In vitro | Benefits in their proliferation capability, but may inhibit differentiation potential. Could have adverse effects for clinical applications, such as tumor formation | [214] |
|
IL-10 HGF IDO Foxp3 incorporation |
hBM-MSC |
In vitro In vivo* |
Attenuates the severity of acute GVHD. Enhanced immunosuppressive properties of MSC. Promotes liver allograft tolerance through the generation of regulatory T cells | [215–218] |
|
Bcl-2 engineered |
hBM-MSC |
In vitro In vivo* |
Better apoptotic tolerance, improved cell survival, VEGF secretion and reduced heart infarct size | [219] |
|
bFGF PDGF-BB TGF-β1 overexpressed |
hBM-MSC | In vitro |
bFGF or PDGF-B lead to highly proliferating MSC and increase osteogenesis. Conversely, adipogenesis is affected. TGF-β1 blocks both osteogenic and adipogenic differentiation, inducing the formation of stress fibers |
[220] |
| PI3K-C2α overexpressed |
BM-MSC rat |
In vitro In vivo* |
The level of apoptotic proteins is downregulated. Increased cell viability of MSC and enhanced myocardial regeneration. Reduction of infarct size and fibrosis area | [221, 222] |
| SDF-1α overexpressed |
BM-MSC rat |
In vitro In vivo* |
MSC differentiation into endothelial cells. Reduction of infarct size and fibrosis. High vascular density and thicker left ventricular wall. Improvement of left ventricular performance | [223] |
| CXCR4 overexpressed | hBM-MSC |
In vitro In vivo* |
Enhanced MSC chemokinesis. Improved cell trafficking and tissue repair. Enhancement of relevant trophic signals. No adverse effects on proliferation and differentiation | [220, 224] |
| HGF overexpressed | hBM-MSC |
In vitro In vivo* |
Inhibited collagen deposition and improved cystometric parameters in bladder outlet obstruction | [225] |
| IGF-I overexpressed |
BM-MSC mice |
In vitro In vivo* |
Paracrine support to EPO-secreting MSC in anemia. Hematocrit elevation. Improvement of Heart function | [226] |
| BDNF overexpressed | hBM-MSC | In vitro | Lentivirally MSC modification provides significantly neuroprotective effect from degeneration compared to native hMSC | [232] |
| IFN-β hMSC engineered | hBM-MSC |
In vitro In vivo* |
In vitro, promotion of tumor cell apoptosis, inhibition of angiogenesis, and increased NK activity In vivo, significantly increased survival in a human U87 intracranial glioma xenograft model. Prolonged survival in a prostate cancer lung metastasis model, compared to controls |
[233, 234] |
| IFN-γ hMSC engineered | hBM-MSC | In vitro | Inhibition of proliferation and induction of apoptosis in leukemia cells | [235] |
| Ad-FKN engineered | adenoviral vector fractalkine gene |
In vitro In vivo* |
Ad-fractalkine mediates antitumor effects by induction of both innate and adaptive immunity | [236] |
| IL-12 expressed | hBM-MSC |
In vitro In vivo* |
Prevention of breast cancer metastasis into the lymph nodes and internal organs as well as increased tumor cell apoptosis and an antiangiogenic effect on tumor stroma | [237] |
| (CRISPR)/Cas9 |
hMESCs BM-MSC |
In vitro In vitro In vivo |
Obtain PAI-1 knockout and PAI-1 overexpressing hMESCs, provides evidence of successful and effective MSCs secretome managing via CRISPR/Cas9 genome editing technology Overexpression of IL-10 in BM-MSCs. Transplantation of BM-MSCs overexpressing IL-10 inhibited inflammatory cell infiltration and pro-inflammatory cytokines production, improved cardiac functional recovery, alleviated cardiac injury, decreased apoptosis of cardiac cells and increased angiogenesis |
[241] [242] |
* animal model