Nerve xenografts to assess cellular expression of the abnormality of myelination in inherited neuropathy and friedreich ataxia

Human sural nerve fascicles from healthy volunteers and patients with inherited hypertrophic neuropathy (HMSN-I and HMSN-Ill, respectively) and with Friedreich ataxia (FA) were transplanted into nude and T-cell-suppressed mouse nerve to determine whether transplanted Schwann cells would express the histologic and myelination abnormalities characteristic of these disorders. Sections above, at, and below the transplant were evaluated by phase and transmission electronmicro-scope (TEM) morphometric analysis at times up to 3 months after transplant. The characteristic structure of the human perineurium and of the onion-bulb formation was maintained, indicating that human Schwann and perineurial cells survive transplantation and express themselves. Myelination in human nerve xenografts was delayed as compared to distal mouse nerve myelination, which may reflect genetic characteristics, delayed vascularization, or physical size of the transplant. A variable number of fibers regrew outside the fascicle, creating a problem in data interpretation, since differences may exist in populations of fibers to be compared in control and disease xenografts and in xenografts and distal mouse nerve. Although xenograft myelination began earlier in controls than in HMSN-Ill, the difference in myelination at 3 months was not significantly different, nor was there a significant difference in onset or degree of myelination in controls, HMSN-I, and FA nerve xenografts at intervals up to 3 months. Lack of significant differences, especially for HMSN-Ill and control nerves, may be attributed to small numbers and insufficient time after transplant. A study of more xenografts, harvested after longer periods of time, will thus be needed before concluding that Schwann cells play no major role in the hypomyelination of HMSN-Ill. Present evidence does not favor a major role of Schwann cells in the segmental demyelination of HMSN I and FA.