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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

  • Nephrology - Original Paper
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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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Authors and Affiliations

  1. Institute of Kidney Diseases & Research Centre and Institute of Transplantation Sciences, Ahmedabad, India

    Aruna V. Vanikar, Hargovind L. Trivedi, A. Feroze, Kamal V. Kanodia, Shruti D. Dave & Pankaj R. Shah

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  1. Aruna V. Vanikar
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  2. Hargovind L. Trivedi
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  3. A. Feroze
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  4. Kamal V. Kanodia
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  5. Shruti D. Dave
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  6. Pankaj R. Shah
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Correspondence to Aruna V. Vanikar.

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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

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