Transplantation of porcine umbilical cord matrix cells into the rat brain.
Immune rejection of transplanted material is a potential complication of organ donation. In response to tissue transplantation, immune rejection has two components: a host defense directed against the grafted tissue and an immune response from the grafted tissue against the host (graft vs host disease). To treat immune rejection, transplant recipients are typically put on immunosuppression therapy. Complications may arise from immune suppression or from secondary effects of immunosuppression drugs. Our preliminary work indicated that stem cells may be xenotransplanted without immunosuppression therapy. Here, we investigated the survival of pig stem cells derived from umbilical cord mucous connective tissue (UCM) after transplantation into rats. Our data demonstrate that UCM cells survive at least 6 weeks without immune suppression of the host animals after transplantation into either the brain or the periphery. In the first experiment, UCM cells were transplanted into the rat brain and recovered in that tissue 2-6 weeks posttransplantation. At 4 weeks posttransplantation, the UCM cells engrafted into the brain along the injection tract. The cells were small and roughly spherical. The transplanted cells were positively immunostained using a pig-specific antibody for neuronal filament 70 (NF70). In contrast, 6 weeks posttransplantation, about 10% of the UCM cells that were recovered had migrated away from the injection site into the region just ventral to the corpus callosum; these cells also stained positively for NF70. In our second experiment, UCM cells that were engineered to constitutively express enhanced green fluorescent protein (eGFP) were transplanted. These cells were recovered 2-4 weeks after brain transplantation. Engrafted cells expressing eGFP and positively staining for NF70 were recovered. This finding indicates a potential for gene therapy. In the third experiment, to determine whether depositing the graft into the brain protected UCM cells from immune detection/clearance, UCM cells were injected into the tail vein and/or the semitendinosis muscle in a group of animals. UCM cells were recovered from the muscle or within the kidney 3 weeks posttransplantation. In control experiments, rat brains were injected with PKH 26-labeled UCM cells that had been lysed by repeated sonic disruption. One and 2 weeks following injection, no PKH 26-labeled neurons or glia were observed. Taken together, these data indicate that UCM cells can survive xenotransplantation and that a subset of the UCM cells respond to local signals to differentiate along a neural lineage.
Weiss
M L
ML
Department of Anatomy and Physiology, Kansas State University, College of Veterinary Medicine, Manhattan, KS 66506-5602, USA. weiss@vet.ksu.edu
Mitchell
K E
KE
Hix
J E
JE
Medicetty
S
S
El-Zarkouny
S Z
SZ
Grieger
D
D
Troyer
D L
DL
D000818:Animals; D001921:Brain / Q000166:cytology*; D002470:Cell Survival; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D006085:Graft Survival; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007267:Injections; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D016900:Neurofilament Proteins / Q000096:biosynthesis; D019635:Neurosurgical Procedures / Q000379:methods; D009930:Organic Chemicals; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013552:Swine; D014162:Transfection; D014470:Umbilical Cord / Q000166:cytology / Q000196:embryology / Q000637:transplantation*
D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D016900:Neurofilament Proteins; D009930:Organic Chemicals; C070080:PKH 26; D049452:Green Fluorescent Proteins