Bank of stem cells for producing cells for transplantation having hla antigens matching those of transplant recipients and methods for making and using such a stem cell bank

Abstract

Methods for producing stem cell banks, preferably human, which optionally may be transgenic, e.g., comprised of homozygous MHC allele cell lines are provided. These cells are produced preferably from parthenogenic, IVF, or same-species or cross-species nuclear transfer embryos or by de-differentiation of somatic cells by cytoplasm transfer. Methods for using these stem cell banks for producing stem and differentiated cells for therapy, especially acute therapies, and for screening for drugs for disease treatment are also provided.

1 - 62 . (canceled) 
     
     
         63 . A method for treatment, preferably acute treatment, comprising transplanting cells or tissue that are homozygous for at least HLA one allele in a person in need of such a transplant, comprising:
 a. identifying the MHC alleles of a person in need of a transplant (the recipient);   b. obtaining from a stem cell bank comprising a plurality of stem cells homozygous for at least one MHC allele of the transplant recipient;   c. generating cells or tissue suitable for transplant from said stem cells; and   d. transplanting said cells or tissue suitable for transplant into said recipient.   
     
     
         64 . The method of  claim 63  wherein said stem cell bank comprises at least 10 different human stem cell lines, wherein each of said stem cell lines are homozygous for a different combination of HLA alleles relative to the other stem cell lines. 
     
     
         65 . The method of  claim 63  wherein said stem cell bank comprises at least 15 different human stem cell lines wherein each of said stem cell lines are homozygous for a different combination of HLA alleles relative to the other human stem cell lines in the cell bank. 
     
     
         66 . The method of  claim 63  wherein said stem cell bank comprises at least about 100 to 1000 stem cell lines each homozygous for a different combination of HLA alleles relative to the other human stem cell lines in the cell bank. 
     
     
         67 . The method of  claim 63  wherein one or more of said human stem cell lines are ES or inner cell mass-derived stem cells. 
     
     
         68 . The method of  claim 63  wherein one or more of said human stem cell lines is derived from a parthenogenetic human embryo. 
     
     
         69 . The method of  claim 63  wherein one or more of said human stem cell lines are produced by haploidization comprising the steps of
 a) inserting or fusing a somatic donor cell or nucleus thereof into or with an oocyte which is treated to remove or destroy its endogenous genomic DNA before, during or after insertion or fusion; 
 b) activation of the reconstructed embryo to expel haploid genome into a pseudopolar body; 
 c) screening of the pseudopolar body for the genetype of the remaining pronuclear; 
 d) combination of the two pronuclei to generate a reconstructured diploid embryo by pronuclear transfer or alternatively producing a diploid embryo by transferal of a pronucleus to an activated haploid oocyte comprising desired haploid genome; 
 e) optionally injecting human morula stage embryo lysates into the reconstructed embryos; and 
 f) isolating human stem cell lines from said reconstructed diploid embryo. 
 
     
     
         70 . The method of  claim 63  wherein one or more of said human stem cell lines is produced by the insertion of first and second polar bodies into a recipient cell. 
     
     
         71 . The method of  claim 63  wherein at least one of said stem cell lines is produced by de-differentiation of a somatic cell by cytoplasmic transfer. 
     
     
         72 . The method of  claim 63  wherein said human stem cell bank comprises cells which are homozygous for one of the following HLA serotypes: HLA-A1, HLA-A3, HLA-A11, HLA-A15, HLA-A22, HLA-A27, HLA-A28, HLA-A29, HLA-A32, HLA-B5, HLA-B7, HLA-B8, HLA-B12, HLA-B17, HLA-B18, HLA-B35 and HLA-B40. 
     
     
         73 . The method of  claim 63  wherein said human stem cell bank comprises stem cells which are homozygous for at least one of the following HLA-A, —B or -DR haplotypes: 1, 7, 2; 1, 8, 3; 2, 14, 1; 2, 35, 4; 2, 35, 8; 2, 44, 4; 3, 7, 2; 3, 7, 4; 3, 7, 8; 3, 35, 1; 31, 51, 4; and 32, 14, 7. 
     
     
         74 . The method of  claim 72  wherein said cell lines are O-negative. 
     
     
         75 . The method of  claim 73  wherein said cell lines are O-negative. 
     
     
         76 . The method of  claim 63 , wherein step b comprises obtaining stem cells selected from the group consisting of totipotent, nearly totipotent, and pluripotent stem cells. 
     
     
         77 . The method of  claim 63 , wherein step b comprises obtaining embryonic stem cells. 
     
     
         78 . The method of  claim 63 , wherein step b comprises obtaining stem cells that can differentiate into hematopoietic stem cells. 
     
     
         79 . The method of  claim 63 , wherein step b comprises obtaining hematopoietic stem cells from the stem cell bank. 
     
     
         80 . The method of  claim 63 , wherein step b comprises obtaining stem cells homozygous for an MHC allele selected from HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, and HLA-DP. 
     
     
         81 . The method of  claim 63 , wherein step b comprises obtaining stem cells homozygous for the MHC alleles encoding HLA-A, HLA-B, and HLA-DR. 
     
     
         82 . The method of  claim 63 , wherein step b comprises obtaining stem cells derived from embryos produced by in vitro fertilization or intracytoplasmic sperm injection. 
     
     
         83 . The method of  claim 63 , wherein step b comprises obtaining diploid stem cells derived from embryos produced by parthenogenesis. 
     
     
         84 . The method of  claim 83 , comprising obtaining diploid stem cells in which all of the MHC alleles are homozygous. 
     
     
         85 . The method of  claim 63 , wherein step b comprises obtaining stem cells derived from embryos produced by cloning by nuclear transfer. 
     
     
         86 . The method of  claim 85 , comprising obtaining rejuvenated stem cells. 
     
     
         87 . The method of  claim 86 , comprising obtaining rejuvenated stem cells having telomeres that are on average at least as long as the telomeres of age-matched control cells of the same type that are not generated by nuclear transfer techniques. 
     
     
         88 . The method of  claim 86 , comprising obtaining rejuvenated stem cells for which the proliferative life-span is at least as long as the proliferative life-span of age-matched control cells of the same type that are not generated by nuclear transfer techniques. 
     
     
         89 . The method of  claim 86 , comprising obtaining rejuvenated stem cells for which the proliferative life-span is longer than the proliferative life-span of age-matched control cells of the same type that are not generated by nuclear transfer techniques. 
     
     
         90 . The method of  claim 86 , comprising obtaining rejuvenated stem cells having EPC-1 activity that is greater than EPC-1 activity in age-matched control cells of the same type that are not generated by nuclear transfer techniques. 
     
     
         91 . The method of  claim 86 , comprising obtaining rejuvenated stem cells having telomerase activity that is greater than telomerase activity in age-matched control cells of the same type that are not generated by nuclear transfer techniques. 
     
     
         92 . The method of  claim 85 , comprising obtaining stem cells comprising non-human mitochondria. 
     
     
         93 . The method of  claim 63 , wherein step b comprises obtaining stem cells having DNA that is genetically modified relative to the DNA of the human donor from which the stem cells are derived. 
     
     
         94 . The method of  claim 92 , comprising obtaining genetically altered stem cells, the DNA of which is modified by adding, modifying, substituting, or deleting one or more DNA sequences. 
     
     
         95 . The method of  claim 93 , comprising obtaining genetically altered stem cells, the DNA of which is modified so as to obtain, increase, decrease, inhibit, or otherwise modify, the expression of a gene that is native to or introduced into said cells, relative to expression of said gene in a control cell without the genetic modification. 
     
     
         96 . The method of  claim 93 , comprising obtaining genetically altered stem cells, the DNA of which is modified by homologous recombination. 
     
     
         97 . The method of  claim 93 , comprising obtaining genetically altered stem cells, the DNA of which is altered to prevent the expression of a gene encoding an antigenic protein that elicits an immune response contributing to rejection. 
     
     
         98 . The method of  claim 96 , comprising genetically altered stem cells, the DNA of which is modified so as to inhibit production of at least one HLA antigen by cells of said cell line. 
     
     
         99 . The method of  claim 96 , comprising genetically altered stem cells, the DNA of which is modified so as to inhibit production of one or more HLA antigens selected from HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, and HLA-DP. 
     
     
         100 . The method of  claim 96 , comprising genetically altered stem cells, the DNA of which is modified so as to inhibit production of β2-microglobulin. 
     
     
         101 . The method of  claim 96 , comprising genetically altered stem cells, the DNA of which is altered by replacing a non-homozygous MHC allele with one that is homozygous. 
     
     
         102 - 133 . (canceled)