Human umbilical cord tissue cells for inhibiting adverse immune response in histocompatibility-mismatched transplantation

摘要

Cell-based compositions and methods of their use to inhibit an adverse immune response such as graft versus host disease or rejection of transplanted tissue in a transplant recipient that is histocompatibility mismatched to the transplant donor are disclosed. The compositions and methods utilize postpartum-derived cells, such as cells derived from the placenta or umbilicus.

主权项

1. A method for inhibiting an adverse immune response in a transplant recipient in need thereof comprising:
(i) identifying a transplant recipient that is histocompatibility-mismatched to a transplant donor, (ii) Identifying a composition of human umbilical cord tissue cells exhibiting a lower stimulation index of naïve CD4+ T-cells, wherein the identification is by mixed lymphocyte reaction (MLR), wherein the MLR comprises (a) a population of lymphocytes allogenic to the transplant recipient and (b) a composition of human umbilical cord tissue cells allogenic to the transplant recipient, wherein the composition of human umbilical cord tissue cells is a homogeneous population of allogeneic umbilicus-derived cells derived from human umbilical cord tissue free of blood, said cells being capable of self-renewal and expansion in culture, wherein the cells are capable of growth in an atmosphere containing oxygen from about 5% to at least about 20%, and wherein said homogeneous population comprise having the following characteristics: (a) potential for at least 40 doublings in culture; (b) production of CD 10, CD 13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A,B,C; (c) lack of production of CD31, CD34, CD45, CD80, CD86, CD117, CD141, CD 178, B7-H2, HLA-G, and HLA-DR,DP,DQ, as detected by flow cytometry; (d) expression of interleukin 8; reticulon 1; and chemokine (C-X-C motif) ligand 3; (e) secretion of MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1b, RANTES, I309, MDC, and TIMP1; and (f) lack of secretion of TGF-beta2, ANG2, PDGFbb, MIP1a, and VEGF, as detected by ELISA, (iii) administering the identified composition of homogenous human umbilical cord tissue cell to the transplant recipient in an amount effective for inhibiting the adverse immune response in the transplant recipient that is histocompatibility-mismatched to the transplant donor, wherein the identified composition inhibits the adverse immune response in the transplant recipient that is histocompatibility-mismatched to the transplant donor.