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Since the generation of buffalo embryonic stem cells (ESCs) from the inner cell mass (ICM) of blastocysts in 2004 to till date, significant progress has been achieved in this species. Derivation and maintenance of ESCs from blastocysts generated by parthenogenesis, in vitro fertilization and nuclear transfer showed a steady progress towards finding the optimal conditions for the derivation of stable and highly competent buffalo ESCs. The molecular mechanisms for self-renewal of buffalo ESCs and the role of various growth factors involved therein as well as differentiation capacity were explored to a great extent. Although some reports showed the successful isolation and long-term culture of buffalo ESCs in vitro, but many studies were not able to establish suitable conditions for preventing spontaneous differentiation and senescence of ESCs. Hence a need to search alternative ways of deriving unipotent …