title: Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study.
abstract: BACKGROUND
  Mesenchymal 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.
  
  
  METHODS
  MSCs 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.
  
  
  RESULTS
  Seven 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.
  
  
  CONCLUSIONS
  Donor 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.
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kmhyj111@skku.edu
authors.forename: Hyunah
authors.initials: H
authors.lastname: Lee
authors.forename: Jae Berm
authors.initials: JB
authors.lastname: Park
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Lee
authors.forename: Soyoung
authors.initials: S
authors.lastname: Baek
authors.forename: HyunSoo
authors.initials: H
authors.lastname: Kim
authors.forename: Sung Joo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D017148:Infusions, Intraosseous; D016753:Interleukin-10 / Q000097:blood; D016030:Kidney Transplantation / Q000379:methods*; D019520:Living Donors; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D010865:Pilot Projects; D051437:Renal Insufficiency / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D016753:Interleukin-10; D003404:Creatinine