Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease

Abstract

The movement disorder in Parkinson's disease results from the selective degeneration of a small group of dopaminergic neurons in the substantia nigra pars compacta region of the brain. A number of exploratory studies using human fetal tissue allografts have suggested that transplantation of dopaminergic neurons may become an effective treatment for patients with Parkinson's disease and the difficulty in obtaining human fetal tissue has generated interest in finding corresponding non-human donor cells. Here we report a post-mortem histological analysis of fetal pig neural cells that were placed unilaterally into the caudate-putamen brain region of a patient suffering from Parkinson's disease. Long-term (over seven months) graft survival was found and the presence of pig dopaminergic neurons and other pig neural and glial cells is documented. Pig neurons extended axons from the graft sites into the host brain. Furthermore, other graft derived cells were observed several millimeters from the implantation sites. Markers for human microglia and T-cells showed only low reactivity in direct proximity to the grafts. This is the first documentation of neural xenograft survival in the human brain and of appropriate growth of non-human dopaminergic neurons for a potential therapeutic response in Parkinson's disease.

The contribution of farm animals to human health

“…Porcine islet cells have been transplanted to diabetic patients and were shown to be at least partially functional over a limited period of time [51]. Porcine fetal neural cells were transplanted into the brain of patients suffering from Parkinson's and Huntington's disease [52,53]. In a single autopsied patient the graft survived for .7 months and the transplanted cells formed dopaminergic neurons and glial cells.…”

Simultaneous inhibition of B7 and LFA‐1 signaling prevents rejection of discordant neural xenografts in mice lacking CD40L

“…No transmission of porcine endogenous retrovirus (PERV) was detected in any of the transplanted patients [11]. Post-mortem analysis of the brain of one deceased patient that died from a pulmonary embolism 7 months after transplantation, revealed 638 surviving transplanted dopamine cells [12]. It is estimated that 80,000 cells is the minimum number required for functional effects to occur [4].…”

Pancreas and Kidney Transplantation Using Embryonic Donor Organs

“…8 In addition, pig neural cells are not subject to hyperacute or acute vascular rejection post-transplantation into humans. 39 As delineated by Cascalho and Platt, 2 cellular transplantation has limitations. First, it is difficult to imagine how functions of structurally complex organs can be enhanced or recapitulated by cells alone.…”