Improved methods of cell therapy are provided using cells and tissues that are histocompatible with a human or non-human mammal transplant recipient. The cells and tissues for transplant produced by the present invention exhibit a youthful state and can be committed to specific cell lineages to better infiltrate and proliferate at a desired target, e.g., a tissue, or organ in need of cell replacement therapy. For providing cells and tissues for transplant to a non-human mammal, the cells and tissues can be isolated from a gastrulating embryo produced by same-species nuclear transfer. Histocompatible cells and tissues for transplant to a human can be isolated from a gastrulating embryo that (i) is genetically modified to be in capable of developing beyond and early stage, or (ii) is produced by cross-species nuclear transfer between a human nuclear donor cell and an enucleated recipient cell, e.g., an oocyte, of a non-human mammal, or (iii) is produced by androgenesis or gynogenesis, or from pluripotent stem cells generated from such an embryo. Methods for producing histocompatible cells and tissues for transplant to a human can also be used to produce such cells or tissues for transplant to non-human mammals. The present invention also provides model embryonic systems having defined genetic makeup that are useful for developing and testing methods for cell and tissue therapy, and for studying genetic imprinting, reprogramming, rejuvenation, and other biochemical, metabolic, and physiological phenomena associated with embryogenesis.
