Gene-engineered mesenchymal stem cells and applications thereof
Accordingly, the present disclosure provides a population of genetically engineered mesenchymal stem cells (MSCs), comprising an expression vector comprising an Akt or HGF gene and a PD-L1 gene. Also provided is a method for synergistically increasing survival status and immunomodulatory ability of an MSC or enhancing proliferation of an MSC, comprising transfecting an MSC with an Akt or HGF gene and a PD-L1 gene and a method for preventing, ameliorating and/or treating an ischemia condition, enhancing neuroregeneration or reducing neuronal death, comprising administering an effective amount of a population of genetically engineered MSCs of the present disclosure to a subject in need thereof.
1 . A population of genetically engineered mesenchymal stem cells (MSCs), wherein the MSCs are transfected with a hepatocyte growth factor (HGF) gene and a PD-L1 gene.
2 . The population of genetically engineered MSCs of claim 1 , wherein the MSCs are umbilical cord mesenchymal stem cells (UMSCs), adipose derived mesenchymal stem cells (ADSCs), or bone marrow mesenchymal stem cells (BMSCs).
3 . The population of genetically engineered MSCs of claim 1 , wherein the HGF gene and the PD-L1 gene are comprised in a vector.
4 . The population of genetically engineered MSCs of claim 3 , wherein the vector is a lentiviral vector.
5 . A pharmaceutical composition comprising the population of genetically engineered MSCs of claim 1 .
6 . A method for making the population of genetically engineered MSCs of claim 1 , comprising transfecting the MSCs with an HGF gene and a PD-L1.
7 . The method of claim 6 , wherein the MSCs are UMSCs, ADSCs or BMSCs.
8 . A method for preventing, ameliorating and/or treating an ischemia condition, enhancing neuroregeneration or reducing neuronal death in a subject in need thereof, comprising administering an effective amount of the population of genetically engineered MSCs of claim 1 to the subject.
9 . The method of claim 8 , wherein the effective amount ranges from about 1×10 5 cells to about 1×10 8 cells.
10 . The method of claim 8 , wherein the administration reduces inflammatory response but enhances accumulation of CD8 + CD122 + Tregs in an ischemic tissue.
11 . The method of claim 10 , wherein the ischemic tissue is an ischemic brain tissue.
12 . The method of claim 8 , wherein the administration increases the expression of regulatory molecules on T cells in the subject.
13 . The method of claim 8 , wherein the ischemia condition is a stroke.
14 . The method of claim 8 , wherein the ischemia condition is myocardial infarction (MI).
15 . The method of claim 14 , wherein the MI is acute myocardial infarction (AMI).
16 . The method of claim 8 , wherein the administration is intravenous injection, intracarotid injection, intraarterial injection, or a combination thereof.
17 . The method of claim 8 , wherein the administration is intracarotid injection in combination with intravenous injection or intraarterial injection in combination with intravenous injection in a subject suffering from a stroke or AMI.
18 . The method of claim 17 , wherein the administration is in an effective amount ranging from about 1×10 4 cells to about 1×10 6 cells for intracarotid injection and about 3×10 4 cells to about 1×10 7 cells for intravenous injection.
19 . The method of claim 8 , wherein the administration attenuates MI-Induced fibrosis, reduces inflammation on ischemic tissue, attenuates post-MI dysfunction and reduces infarct size after MI; increases the expression of regulatory molecules on T cells in spleens after a stroke; or reduces neuronal death from stroke brain damage.