Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study

Abstract

BackgroundMesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow.MethodsMSCs were derived from negative HLA cross-match donors. Donor bone marrow was harvested 5 weeks prior to KT. At the time of transplantation, 1 x 106 cell/kg of donor MSC was directly injected into the bone marrow of the recipient’s right iliac bone. Patients’ clinical outcomes, presence of mixed chimerism by short tandem repeat polymerase chain reaction, analysis of plasma FoxP3 mRNA and cytokine level, and mixed lymphocyte reaction (MLR) were performed.ResultsSeven patients enrolled in this study and received donor MSC injections simultaneously with LDKT. The median age of recipients was 36 years (32 ~ 48). The number of HLA mismatches was 3 or less in 5 and more than 3 in 2. No local complications or adverse events such as hypersensitivity occurred during or after the injection of donor MSC. There was no graft failure, but the biopsy-proven acute rejections were observed in 3 recipients during the follow-up period controlled well with steroid pulse therapy (SPT). The last serum creatinine was a median of 1.23 mg/dL (0.83 ~ 2.07). Mixed chimerism was not detected in the peripheral blood of the recipients at 1 and 8 week of post-transplantation. Donor-specific lymphocyte or T cell proliferation and Treg priming responses were observed in some patients. Plasma level of IL-10, a known mediator of MSC-induced immune suppression, increased in the patients with Treg induction.ConclusionDonor MSC injection into the iliac bone at the time of KT was feasible and safe. A possible correlation was observed between the induction of inhibitory immune responses and the clinical outcome in the MSC-kidney transplanted patients. Further research will be performed to evaluate the efficacy of MSC injection for the induction of mixed chimerism and subsequent immune tolerance in KT.

Mesenchymal stromal (stem) cells to improve solid organ transplant outcome

“…Multiple MSC clinical trials in SOT are registered with ClinicalTrials.gov ( Table 2 )(3, 5, 7, 8), but the overall worldwide number is likely higher (4, 9). The results from recent MSC trials in SOT are encouraging ( Table 3 ).…”

The use of mesenchymal stromal cells in solid organ transplantation

“…The procedure was safe, but three patients had biopsy-proven acute rejection that was controlled with corticosteroid pulse therapy. Donor-specific T cell proliferation was observed in two patients, while Treg priming responses were observed in two others associated with increased IL-10 levels in the peripheral blood [40]. 6 /kg administered at the time of kidney graft reperfusion and 2 weeks later plus either low-dose or standarddose CNI treatment.…”

Untitled

“…Recently, there was a report on intraosseous donor mesenchymal stem cells for living-donor kidney transplant. 19 Induction therapy with autologous MSCs may be effective for related living-donor kidney transplant. 7 Induction with MSCs plus IL-2 receptor antibody was associated with lower incidence of rejection and with lower complications, such as leukopenia and infections.…”