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Background The loss of perspiration after a massive deep burn hampers the survivor to lead a life of high quality, as they are deprived the function of regulating body temperature through perspiration during sultry months. With maturation of science of burn care, the number of survivors is increased, therefore, it is imperative that this problem should be tackled in order to improve their quality of life. Objective To explore the possibility of transdifferentiating bone marrow mesenchymal stem cells (MSCs) into sweat gland cells (SGCs), and implanting the latter into fresh skin wound to generate functional sweat glands. Methods Human bone marrow MSCs and SGCs were isolated from the same patients. They were identified with specific markers, and then co-cultured. The stem cells which subsequently exhibited the phenotype of sweat gland cells were implanted into scald injured paws of nude mice, and regeneration of functioning sweat glands was confirmed by perspiration test (iodine and starch) and histological examination. A male patient bearing almost iden- tical burn scars on the posterior aspect of both arms was enrolled for clinical trial. The scars were first proved to be anhydrotic with iodine and starch test. With patient's written consent, the clinical trial was carried out. Bone marrow MSCs and sweat gland cells were obtained from the patient. After being heat shocked, the SGCs were co-cultured with MSCs. Three days later, the scars of both arms were excised. MSCs having acquired the phenotype of sweat gland cells after co-culture were evenly spread onto the excision wound on the right arm. They were covered with a piece of acellular allogeneic dermis, which was perforated with numerous micropores. On top of the latter, micrografts of autologous origin were transplanted, and the wound was finally covered with a piece of allogeneic skin graft. The wound on the left side was similarly covered, but without transdifferentiated MSCs. After complete healing of the wounds, perspiration test with iodine and starch was performed, and biopsy was taken from the MSCs transplanted area. The components of the sweat collected from the implantation area were analyzed and compared with that from normal skin elsewhere on the body. The same procedure was performed in a girl patient with a chin-neck contracture. The scar was totally excised, and into one third of the excision wound in vitro transdifferentiated MSCs were implanted similar to the above patient. The examinations were repeated after wound healed. Results In the animal experiment, it was shown that there was regeneration of functional sweat glands in the burned paws of the nude mice. In human patients, all wounds healed nicely. The areas where transdifferented MSCs were implanted showed positive iodine-starch perspiration test. Histological and immunohistochemical examination confirmed that the transformed MSCs bore the specific marker carcinoembryonic antigen (CEA) of sweat gland cells. Biochemical analysis of the excreted sweat contained similar components as that of sweat collected from normal skin. Conclusions MSCs can be transdifferentiated into SGCs in vitro, and they can be implanted into a fresh wound to form functional sweat glands. However, enormous amount of work should be done before the same result would be realized in patients with massive deep burn within a short duration after the injury, so that the patients could regain the function of perspiration after surviving the massive loss of normal skin.