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Despite being a miracle of modern medicine, solid organ transplant recipients are always at risk of rejection, and remain dependent on lifelong immunosuppression. Currently used immunosuppressive drugs suppress the potential of immune system and interfere with the metabolism of medications. Cellular therapies currently being investigated for this purpose require the use of ablative radiotherapy. The investigators are using a less toxic strategy by harnessing the immunosuppressive potential of the MSCs in the Kidney Transplant (KTx) recipients and studying immunomodulation mediated by these cells in the KTx patients.
Hypothesis MSCs interfere with signalling of Immune cells like T cells, B cells and Dendritic cells which leads to improve graft survival of renal transplant patients.
Aim To investigate effect of MSCs on immune cell repertoire in a donor specific mediated response.
The investigators aim to collect peripheral blood from 30 patients (10 patients for autologous cell infusion and 10 for allogeneic (donor derived cell infusion) at various time intervals following MSC therapy. 10 patients serve as controls on standard dose of drugs but without MSC infusion. This peripheral blood would be utilized for isolation of mononuclear cells and performing various immune assays on these cells in a donor specific response.
This is an open label type of study having 3 groups of patients: 1st group comprising of patients that would undergo allogeneic (donor-derived) mesenchymal stem cell infusion, 2nd group that would undergo autologous (patient-derived) mesenchymal stem cells and the third group (control group) without any stem cell infusion. All the three groups would have standard dose of Immunosuppressive drugs. Initially the investigators want to recruit 10 patients in each group and would increase the group size if the investigators get promising results on the follow up. The investigators plan to follow up the patients upto 1-2 years for immune based assays and then continue the follow up for atleast 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Autologus Mesenchymal Stem Cells | Experimental | This group would get two doses of mesenchymal stem cell (MSCs) infusion, one day pre transplant and 30 days post transplant. These MSCs would be derived from transplant recipient's bone marrow which are cultured in GMP compliant laboratories for 4-6 weeks. |
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| Allogeniec Mesenchymal Stem Cells | Active Comparator | This group would get two doses of mesenchymal stem cell (MSCs) infusion, one day pre transplant and 30 days post transplant. These MSCs would be derived from transplant donor's bone marrow which are cultured in GMP compliant laboratories for 4-6 weeks. |
|
| Control without Mesenchymal Stem Cells | No Intervention | This group would get no stem cell infusion. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mesenchymal Stem Cells | Biological | These Mesenchymal stem cells are derived from bone marrow of either renal transplant patients or their donors depending upon the group of study. |
| Measure | Description | Time Frame |
|---|---|---|
| Expansion of regulatory T cell compartment of the patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients. | 6 months | |
| Normalization of serum creatinine levels of the patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| T cell proliferation changes in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients. | 0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation | |
| Changes in regulatory T cells in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Aruna Rakha, PhD. | PGIMER, Chandigarh, India | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Translational and Regenerative Medicine | Chandigarh | Chandigarh | 160012 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25230334 | Background | Mudrabettu C, Kumar V, Rakha A, Yadav AK, Ramachandran R, Kanwar DB, Nada R, Minz M, Sakhuja V, Marwaha N, Jha V. Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation: a pilot study. Nephrology (Carlton). 2015 Jan;20(1):25-33. doi: 10.1111/nep.12338. | |
| 25173397 |
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|
| 0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation |
| Changes in memory T cells in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients. | 0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation |
| Changes in B cells in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients. | 0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation |
| Changes in cytokine profile in patients undergoing renal transplant and infused with mesenchymal stem cells as compared to the control patients. | 0day (one day before transpnatation), 30 days, 90days, 180 days, 1year, 2year post transplantation |
| Rakha A, Todeschini M, Casiraghi F. Assessment of anti-donor T cell proliferation and cytotoxic T lymphocyte-mediated lympholysis in living donor kidney transplant patients. Methods Mol Biol. 2014;1213:355-64. doi: 10.1007/978-1-4939-1453-1_29. |