ADVANCES OF PRECLINICAL RESEARCH IN XENOGENEIC (PORCINE) CELL TRANSPLANTATION_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

ZHOUXiaonan , WUYanshuang ,  LEILei

Department of Histology and Embryology, Harbin Medical University, Harbin Heilongjiang, 150081, P. R. China;

Corresponding author：

LEILei, Email: leiys2002@yahoo.com

Keywords：

Xenogeneic cell transplantation; Immune rejection; Porcine-derived cells

DOI：

10.7507/1002-1892.20140332

Video：

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Objective To summarize the advances of precl inical research in xenogeneic (porcine) cell transplantation in recent years. Methods The literature about the precl inical research in xenogeneic (porcine) cell transplantation was analyzed and summarized. Results With the application of new immunosuppressive agents and the generation of transgenic pigs, great progress has been achieved in xenogeneic transplantation of pig-derived nerve cells, islet cells, liver cells, and various types of stem cells. The survival time of xenogeneic cell (porcine) significantly prolonged, but there is still a long way to go before cl inical application. Conclusion The source of xenogeneic (porcine) cells is abundant and the experiments are reproducible. However, how to effectively prevent rejection and prolong the survival time in the host, and avoid the spread of virus between species are still need to be solved in the future research.

Citation： ZHOUXiaonan, WUYanshuang, LEILei. ADVANCES OF PRECLINICAL RESEARCH IN XENOGENEIC (PORCINE) CELL TRANSPLANTATION. Chinese Journal of Reparative and Reconstructive Surgery, 2014, 28(12): 1536-1539. doi: 10.7507/1002-1892.20140332 Copy

1.	Ekser B, Ezzelarab M, Hara H, et al. Clinical xenotransplantation:the next medical revolution? Lancet, 2012, 379(9816):672-683.
2.	Luo Y, Lin L, Bolund L, et al. Genetically modified pigs for biomedical research. J Inherit Metab Dis, 2012, 35(4):695-713.
3.	Tseng YL, Sachs DH, Cooper DK. Porcine hematopoietic progenitor cell transplantation in nonhuman primates:a review of progress. Transplantation, 2005, 79(1):1-9.
4.	Li J, Ezzelarab MB, Cooper DK. Do mesenchymal stem cells function across species barriers? Relevance for xenotransplantation. Xenotransplantation, 2012, 19(5):273-285.
5.	Lin CS, Lin G, Lue TF. Allogeneic and xenogeneic transplantation of adipose-derived stem cells in immunocompetent recipients without immunosuppressants. Stem Cells Dev, 2012, 21(15):2770-2778.
6.	Lévêque X, Nerrière-Daguin V, Neveu I, et al. Pig neural cells derived from foetal mesencephalon as cell source for intracerebral xenotransplantation. Methods Mol Biol, 2012, 885:233-243.
7.	Deacon T, Schumacher J, Dinsmore J, et al. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease. Nat Med, 1997, 3(3):350-353.
8.	Muldoon LL, Alvarez JI, Begley DJ, et al. Immunologic privilege in the central nervous system and the blood-brain barrier. J Cereb Blood Flow Metab, 2013, 33(1):13-21.
9.	Krystkowiak P, Gaura V, Labalette M, et al. Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington's disease. PLoS One, 2007, 2(1): e166.
10.	Martin C, Plat M, Nerriére-Daguin V, et al. Transgenic expression of CTLA4-Ig by fetal pig neurons for xenotransplantation. Transgenic Res, 2005, 14(4):373-384.
11.	Badin RA, Padoan A, Vadori M, et al. Long-term cl inical recovery in parkinsonian monkey reci pients of CTLA4-Ig transgenic porcine neural precursors. Transplantation, 2010, 90(Suppl 2):47.
12.	Ricordi C, Finke EH, Lacy PE. A method for the mass isolation of islets from the adult pig pancreas. Diabetes, 1986, 35(6):649-653.
13.	Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med, 2000, 343(4):230-238.
14.	Hammerman MR. Xenotransplantation of embryonic pig pancreas for treatment of diabetes mellitus in non-human primates. J Biomed Sci Eng, 2013, 6(5A). doi:10. 4236/jbise. 2013. 65A002.
15.	Hering BJ, Wijkstrom M, Graham ML, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med, 2006, 12(3):301-303.
16.	Tseng YL, Moran K, Dor FJ, et al. El icited antibodies in baboons exposed to tissues from alpha1, 3-galactosyltransferase gene-knockout pigs. Transplantation, 2006, 81(7):1058-1062.
17.	Zhai C, Yu L, Zhu H, et al. Porcine CTLA4-Ig prolong islet xenografts in rats by downregulating the direct pathway of T-cell activation. Xenotransplantation, 2011, 18(1):40-45.
18.	Sasikala M, Rao GV, Vijayalakshmi V, et al. Long-term functions of encapsulated islets grafted in nonhuman primates without immunosuppression. Transplantation, 2013, 96(7):624-632.
19.	Neufeld T, Ludwig B, Barkai U, et al. The efficacy of an immunoisolating membrane system for islet xenotransplantation in minipigs. PLoS One, 2013, 8(8):e70150.
20.	Dufrane D, Gianello P. Macro- or microencapsulation of pig islets to cure type 1 diabetes. World J Gastroenterol, 2012, 18(47):6885-6893.
21.	Meier RP, Seebach JD, Morel P, et al. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow. PLoS One, 2014, 9(3):e91268.
22.	Dhawan A, Strom SC, Sokal E, et al. Human hepatocyte transplantation. Methods Mol Biol, 2010, 640:525-534.
23.	Fitzpatrick E, Mitry RR, Dhawan A. Human hepatocyte transplantation: state of the art. J Intern Med, 2009, 266(4):339-357.
24.	Mitry RR, Dhawan A, Hughes RD, et al. One liver, three reci pients: segment IV from spl it-l iver procedures as a source of hepatocytes for cell transplantation. Transplantation, 2004, 77(10):1614-1616.
25.	Bonavita AG, Quaresma K, Cotta-de-Almeida V, et al. Hepatocyte xenotransplantation for treating liver disease. Xenotransplantation, 2010, 17(3):181-187.
26.	Nagata H, Nishitai R, Shirota C, et al. Prolonged survival of porcine hepatocytes in cyno-molgus monkeys. Gastroenterology, 2007, 132(1): 321-329.
27.	Mei J, Sgroi A, Mai G, et al. Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in. Cell Transplant, 2009, 18(1):101-110.
28.	Ezzelarab M, Ayares D, Cooper DK. The potential of genetically-modified pig mesenchymal stromal cells in xenotransplantation. Xenotransplantation, 2010, 17(1):3-5.
29.	Ezzelarab M, Ezzelarab C, Wilhite T, et al. Genetically-modified pig mesenchymal stromal cells:xenoantigenicity and effect on human Tcell xenoresponses. Xenotransplantation, 2011, 18(3):183-195.
30.	Nakamura Y, Wang X, Xu C, et al. Xenotransplantation of long-termcultured swine bone marrow-derived mesenchymal stem cells. Stem Cells, 2007, 25(3):612-620.
31.	Eguchi H, Kuroiwa Y, Matsui A, et al. Intra-bone marrow cotransplantation of donor mesenchymal stem cells in pig-to-NOD/SCID mouse bone marrow transplantation facil itates short-term xenogeneic hematopoietic engraftment. Transplant Proc, 2008, 40(2):574-577.
32.	Sablinski T, Emery DW, Monroy R, et al. Long-term discordant xenogeneic (porcine-to-primate) bone marrow engraftment in a monkey treated with porcine-specific growth factors. Transplantation, 1999, 67(7):972-977.
33.	Tseng YL, Dor FJ, Kuwaki K, et al. Bone marrow transplantation from alpha1, 3-galactosyltransferase gene-knockout pigs in baboons. Xenotransplantation, 2004, 11(4):361-370.
34.	Aust L, Devlin B, Foster SJ, et al. Yield of human adi pose-derived adult stem cells from li posuction aspirates. Cytotherapy, 2004, 6(1):7-14.
35.	Gronthos S, Franklin DM, Leddy HA, et al. Surface protein characterization of human adi pose tissue-derived stromal cells. J Cell Physiol, 2001, 189(1):54-63.
36.	Cui L, Yin S, Liu W, et al. Expanded adi pose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2. Tissue Eng, 2007, 13(6):1185-1195.
37.	Niemeyer P, Vohrer J, Schmal H, et al. Survival of human mesenchymal stromal cells from bone marrow and adi pose tissue after xenogenic transplantation in immunocompetent mice. Cytotherapy, 2008, 10(8):784-795.
38.	Kang SK, Lee DH, Bae YC, et al. Improvement of neurological deficits by intracerebral transplantation of human adi pose tissue-derived stromal cells after cerebral ischemia in rats. Exp Neurol, 2003, 183(2):355-366.
39.	Ghasemi N, Razavi S, Mardani M, et al. Transplantation of human adi pose-derived stem cells enhances remyel ination in lysolecithininduced focal demyelination of rat spinal cord. Mol Biotechnol, 2014, 56(5):470-478.
40.	Zhu W, Shi XL, Xiao JQ, et al. Effects of xenogeneic adi pose-derived stem cell transplantation on acute-on-chronic liver failure. Hepatobil iary Pancreat Dis Int, 2013, 12(1):60-67.
41.	Lee K, Kwon DN, Ezashi T, et al. Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency. Proc Natl Acad Sci U S A, 2014, 111(20):7260-7265.

1. Ekser B, Ezzelarab M, Hara H, et al. Clinical xenotransplantation:the next medical revolution? Lancet, 2012, 379(9816):672-683.
2. Luo Y, Lin L, Bolund L, et al. Genetically modified pigs for biomedical research. J Inherit Metab Dis, 2012, 35(4):695-713.
3. Tseng YL, Sachs DH, Cooper DK. Porcine hematopoietic progenitor cell transplantation in nonhuman primates:a review of progress. Transplantation, 2005, 79(1):1-9.
4. Li J, Ezzelarab MB, Cooper DK. Do mesenchymal stem cells function across species barriers? Relevance for xenotransplantation. Xenotransplantation, 2012, 19(5):273-285.
5. Lin CS, Lin G, Lue TF. Allogeneic and xenogeneic transplantation of adipose-derived stem cells in immunocompetent recipients without immunosuppressants. Stem Cells Dev, 2012, 21(15):2770-2778.
6. Lévêque X, Nerrière-Daguin V, Neveu I, et al. Pig neural cells derived from foetal mesencephalon as cell source for intracerebral xenotransplantation. Methods Mol Biol, 2012, 885:233-243.
7. Deacon T, Schumacher J, Dinsmore J, et al. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease. Nat Med, 1997, 3(3):350-353.
8. Muldoon LL, Alvarez JI, Begley DJ, et al. Immunologic privilege in the central nervous system and the blood-brain barrier. J Cereb Blood Flow Metab, 2013, 33(1):13-21.
9. Krystkowiak P, Gaura V, Labalette M, et al. Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington's disease. PLoS One, 2007, 2(1): e166.
10. Martin C, Plat M, Nerriére-Daguin V, et al. Transgenic expression of CTLA4-Ig by fetal pig neurons for xenotransplantation. Transgenic Res, 2005, 14(4):373-384.
11. Badin RA, Padoan A, Vadori M, et al. Long-term cl inical recovery in parkinsonian monkey reci pients of CTLA4-Ig transgenic porcine neural precursors. Transplantation, 2010, 90(Suppl 2):47.
12. Ricordi C, Finke EH, Lacy PE. A method for the mass isolation of islets from the adult pig pancreas. Diabetes, 1986, 35(6):649-653.
13. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med, 2000, 343(4):230-238.
14. Hammerman MR. Xenotransplantation of embryonic pig pancreas for treatment of diabetes mellitus in non-human primates. J Biomed Sci Eng, 2013, 6(5A). doi:10. 4236/jbise. 2013. 65A002.
15. Hering BJ, Wijkstrom M, Graham ML, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med, 2006, 12(3):301-303.
16. Tseng YL, Moran K, Dor FJ, et al. El icited antibodies in baboons exposed to tissues from alpha1, 3-galactosyltransferase gene-knockout pigs. Transplantation, 2006, 81(7):1058-1062.
17. Zhai C, Yu L, Zhu H, et al. Porcine CTLA4-Ig prolong islet xenografts in rats by downregulating the direct pathway of T-cell activation. Xenotransplantation, 2011, 18(1):40-45.
18. Sasikala M, Rao GV, Vijayalakshmi V, et al. Long-term functions of encapsulated islets grafted in nonhuman primates without immunosuppression. Transplantation, 2013, 96(7):624-632.
19. Neufeld T, Ludwig B, Barkai U, et al. The efficacy of an immunoisolating membrane system for islet xenotransplantation in minipigs. PLoS One, 2013, 8(8):e70150.
20. Dufrane D, Gianello P. Macro- or microencapsulation of pig islets to cure type 1 diabetes. World J Gastroenterol, 2012, 18(47):6885-6893.
21. Meier RP, Seebach JD, Morel P, et al. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow. PLoS One, 2014, 9(3):e91268.
22. Dhawan A, Strom SC, Sokal E, et al. Human hepatocyte transplantation. Methods Mol Biol, 2010, 640:525-534.
23. Fitzpatrick E, Mitry RR, Dhawan A. Human hepatocyte transplantation: state of the art. J Intern Med, 2009, 266(4):339-357.
24. Mitry RR, Dhawan A, Hughes RD, et al. One liver, three reci pients: segment IV from spl it-l iver procedures as a source of hepatocytes for cell transplantation. Transplantation, 2004, 77(10):1614-1616.
25. Bonavita AG, Quaresma K, Cotta-de-Almeida V, et al. Hepatocyte xenotransplantation for treating liver disease. Xenotransplantation, 2010, 17(3):181-187.
26. Nagata H, Nishitai R, Shirota C, et al. Prolonged survival of porcine hepatocytes in cyno-molgus monkeys. Gastroenterology, 2007, 132(1): 321-329.
27. Mei J, Sgroi A, Mai G, et al. Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in. Cell Transplant, 2009, 18(1):101-110.
28. Ezzelarab M, Ayares D, Cooper DK. The potential of genetically-modified pig mesenchymal stromal cells in xenotransplantation. Xenotransplantation, 2010, 17(1):3-5.
29. Ezzelarab M, Ezzelarab C, Wilhite T, et al. Genetically-modified pig mesenchymal stromal cells:xenoantigenicity and effect on human Tcell xenoresponses. Xenotransplantation, 2011, 18(3):183-195.
30. Nakamura Y, Wang X, Xu C, et al. Xenotransplantation of long-termcultured swine bone marrow-derived mesenchymal stem cells. Stem Cells, 2007, 25(3):612-620.
31. Eguchi H, Kuroiwa Y, Matsui A, et al. Intra-bone marrow cotransplantation of donor mesenchymal stem cells in pig-to-NOD/SCID mouse bone marrow transplantation facil itates short-term xenogeneic hematopoietic engraftment. Transplant Proc, 2008, 40(2):574-577.
32. Sablinski T, Emery DW, Monroy R, et al. Long-term discordant xenogeneic (porcine-to-primate) bone marrow engraftment in a monkey treated with porcine-specific growth factors. Transplantation, 1999, 67(7):972-977.
33. Tseng YL, Dor FJ, Kuwaki K, et al. Bone marrow transplantation from alpha1, 3-galactosyltransferase gene-knockout pigs in baboons. Xenotransplantation, 2004, 11(4):361-370.
34. Aust L, Devlin B, Foster SJ, et al. Yield of human adi pose-derived adult stem cells from li posuction aspirates. Cytotherapy, 2004, 6(1):7-14.
35. Gronthos S, Franklin DM, Leddy HA, et al. Surface protein characterization of human adi pose tissue-derived stromal cells. J Cell Physiol, 2001, 189(1):54-63.
36. Cui L, Yin S, Liu W, et al. Expanded adi pose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2. Tissue Eng, 2007, 13(6):1185-1195.
37. Niemeyer P, Vohrer J, Schmal H, et al. Survival of human mesenchymal stromal cells from bone marrow and adi pose tissue after xenogenic transplantation in immunocompetent mice. Cytotherapy, 2008, 10(8):784-795.
38. Kang SK, Lee DH, Bae YC, et al. Improvement of neurological deficits by intracerebral transplantation of human adi pose tissue-derived stromal cells after cerebral ischemia in rats. Exp Neurol, 2003, 183(2):355-366.
39. Ghasemi N, Razavi S, Mardani M, et al. Transplantation of human adi pose-derived stem cells enhances remyel ination in lysolecithininduced focal demyelination of rat spinal cord. Mol Biotechnol, 2014, 56(5):470-478.
40. Zhu W, Shi XL, Xiao JQ, et al. Effects of xenogeneic adi pose-derived stem cell transplantation on acute-on-chronic liver failure. Hepatobil iary Pancreat Dis Int, 2013, 12(1):60-67.
41. Lee K, Kwon DN, Ezashi T, et al. Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency. Proc Natl Acad Sci U S A, 2014, 111(20):7260-7265.

Chinese Journal of Reparative and Reconstructive Surgery

ADVANCES OF PRECLINICAL RESEARCH IN XENOGENEIC (PORCINE) CELL TRANSPLANTATION

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