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Isolation and infusion of donor CD34+ bone marrow cells in cadaver kidney transplantation
L De Pauw1, D Abramowicz, V Donckier
1Department of Nephrology-Dialysis-Transplantation, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Insights
Infusion of CD34+ stem cells in kidney transplants is safe, with most patients avoiding acute rejection. However, this therapy did not establish long-term chimerism in recipients.
Area of Science:
- Immunology
- Transplantation Medicine
- Stem Cell Biology
Background:
- Bone marrow cell infusion can induce tolerance in allograft models.
- CD34+ stem cells from human bone marrow may possess tolerogenic properties.
Purpose of the Study:
- To evaluate the safety and efficacy of infusing donor CD34+ stem cells in kidney transplant recipients.
- To assess the potential for inducing tolerance and chimerism post-transplantation.
Main Methods:
- CD34+ stem cells were isolated from cadaveric donor bone marrow.
- Ten kidney transplant recipients received donor CD34+ cells during surgery with OKT3 induction therapy.
- Chimerism was monitored using PCR for donor-specific HLA alleles.
Main Results:
- CD34+ stem cell infusion was well-tolerated in all patients.
- Five patients experienced no acute rejection episodes within 47-325 days post-transplant.
- The remaining five patients had one episode of acute, corticosensitive rejection.
- Long-term chimerism was not detected in seven patients assessed.
Conclusions:
- Infusion of donor CD34+ stem cells appears safe for kidney transplantation.
- The clinical benefit and potential for inducing tolerance require further investigation.
Background:
Infusion of donor bone marrow cells induces tolerance in allograft models. CD34+ stem cells present in human bone marrow could be endowed with tolerogenic properties.
Methods:
CD34+ stem cells were isolated from bone marrow extracted from vertebral bodies of cadaveric donors. Donor CD34+ cells (0.6-3.7 x 10(6)/kg) were infused during surgery in 10 kidney transplant recipients receiving OKT3 as induction therapy. Chimerism was investigated using nested PCR for donor-specific HLA alleles.
Results:
The infusion of CD34+ stem cells was perfectly tolerated. Five patients remained free of acute rejection at follow-up, 47-325 days post-operatively. The five other patients underwent a single episode of corticosensitive acute rejection. Long-term chimerism was not induced in the seven patients investigated for the persistence of donor DNA.
Conclusions:
Infusion of donor CD34+ stem cells in kidney transplantation is safe. The clinical usefulness of the procedure remains to be established.