Abstract
Introduction
We evaluated donor hypo-responsiveness in renal allograft recipients to donor adipose tissue-derived mesenchymal stem cell (h-AD-MSC) +hematopoietic stem cell transplantation (HSCT) vs. HSCT alone.
Methods
Patients were divided into 2 demographically equal groups (n = 100) A and B subjected to equal non-myeloablative conditioning of target-specific irradiation, anti-T + B cell antibodies and cyclophosphamide with HSCT. Group A was administered h-AD-MSC additionally. Transplantation was performed following favorable cross-matching. Cyclosporine, 3 mg/kg BW/day + prednisone, 20 mg/day were immunosuppressants for first 3 months, cyclosporine was replaced by azathioprine subsequently and prednisone lowered to 5–10 mg/day. Peripheral blood chimerism (PBC) was studied using fluorescent in situ hybridization technique at 3/18 months post transplant. Biopsy was performed for graft dysfunction and reported as per Banff criteria,’05.
Results
Mean nucleated HSC counts (n × 108/kgBW) was 7.32 with mean CD34+ yield 0.09% in group A; and 6.98 and 0.40% in group B, respectively; CD45−/90+ was 13.49% in former. Over 18 months post transplant, former had mean serum creatinine (SCr), 1.59 mg%, 12% acute rejection (AR) episodes, 3% patient, 1% patient +graft loss; latter had mean SCr 1.49 mg%, 18% AR episodes, 1% patient, 6% graft and 8% patient +graft losses. PBC was higher (4%) in former than later (1.8%).
Conclusion
Combined h-AD-MSC +HSCT under non-myeloablative conditioning was safe, more effective than HSCT alone to achieve donor hypo-responsiveness with adequate stable graft function and reduced rejection episodes.
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Abbreviations
- BM:
-
Bone marrow
- BMT:
-
Bone marrow transplantation
- FITC:
-
Fluorescein isothiocynate
- G-CSF:
-
Granulocyte colony stimulating factor
- GM-CSF:
-
Granulocyte-macrophage colony stimulating factor
- GVHD:
-
Graft versus host disease
- h-AD:
-
Human adipose tissue
- HLA:
-
Human leukocyte antigen
- HSC:
-
Hematopoietic stem cell
- HSCT:
-
Hematopoietic stem cell transplantation
- MSC:
-
Mesenchymal stem cells
- PE:
-
Phycoerythrin
- PBSC:
-
Peripheral blood stem cell
- SC:
-
Stem cell
- SCr:
-
Serum creatinine
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Vanikar, A.V., Trivedi, H.L., Feroze, A. et al. Effect of co-transplantation of mesenchymal stem cells and hematopoietic stem cells as compared to hematopoietic stem cell transplantation alone in renal transplantation to achieve donor hypo-responsiveness. Int Urol Nephrol 43, 225–232 (2011). https://doi.org/10.1007/s11255-009-9659-1
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DOI: https://doi.org/10.1007/s11255-009-9659-1