Current Status and Future Perspectives of Xenotransplantation

Chung-Gyu Park; Jung-Sik Kim; Jun-Seop Shin; Yong-Hee Kim; Sang-Joon Kim

doi:10.4285/jkstn.2009.23.3.203

Journal List > J Korean Soc Transplant > v.23(3) > 1034291

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Park, Kim, Shin, Kim, and Kim: Current Status and Future Perspectives of Xenotransplantation

Review Article

J Korean Soc Transplant 2009;23(3):203-213.

Published online: 11 January 2009

DOI: https://doi.org/10.4285/jkstn.2009.23.3.203

Current Status and Future Perspectives of Xenotransplantation

Chung-Gyu Park, M.D.^1,2,3,4,^1,2,3,4,^1,2,3,4,^1,2,3,4,, Jung-Sik Kim, Ph.D.^1,2,3,4,^1,2,3,4,^1,2,3,4,^1,2,3,4, Jun-Seop Shin, Ph.D.^1,2,3,4,^1,2,3,4,^1,2,3,4,^1,2,3,4, Yong-Hee Kim, M.D.^1,2,3,4,^1,2,3,4,^1,2,3,4,^1,2,3,4, Sang-Joon Kim, M.D.^2,⁵

¹Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea

²Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea

³Transplantation Research Institute SNUMRC, Seoul National University College of Medicine, Seoul, Korea

⁴Cancer Research Institute and TIMRC, Seoul National University College of Medicine, Seoul, Korea

⁵Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

책임저자：박정규, 서울시 종로구 대학로 103 서울대학교 의과대학 미생물학교실, 110-799 Tel: 02-740-8308, Fax: 02-743-0881 E-mail: chgpark@snu.ac.kr

Received 18 December 2009 Accepted 22 December 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Xenotransplantation using pigs as the transplant source holds great promise to resolve the severe shortage of human organ donors. Although stem-cell-derived organ and tissue regeneration have a potential to solve this as well for the future, it still remains as very early experimental phase. Likewise, artificial organs and mechanical devices have been simply used for bridge therapy to transplant. Therefore, xenotransplantation might provide the most imminent solution to the scarcity of human organ donors. In the last two decades, major progress has been made in understanding the mechanisms of xenografts rejection, zoonotic infections including porcine endogenous retrovirus (PERV) and production of genetically engineered pigs including α1,3-galactosyltransferase-deficient pigs. With these elaborations, it is now on the threshold of first clinical application. Particularly promising first target is porcine pancreatic islet xenotransplantation. Graft survival has been prolonged to almost one year in the non-human primate study and is waiting for the development of relatively non-toxic or clinically applicable immunosuppressive or tolerance-inducing regimens. This review highlights the currently known obstacles to translate xenotransplantation into clinical therapies and the possible strategies to overcome these hurdles, as well as current status and future perspective for clinical xenotransplantaion.

Keywords: Xenotransplantation, Porcine, Islet transplantation, Transplant rejection, Immune tolerance

REFERENCES

1). Groth CG, Korsgren O, Tibell A, Tollemar J, Möller E, Bolinder J, et al. Transplantation of porcine fetal pancreas to diabetic patients. Lancet. 1994; 344:1402–4.

2). Rood PP, Cooper DK. Islet xenotransplantation: are we really ready for clinical trials? Am J Transplant. 2006; 6:1269–74.

3). Hering BJ, Cooper DK, Cozzi E, Schuurman HJ, Korbutt GS, Denner J, et al. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes– executive summary. Xenotransplantation. 2009; 16:196–202.

4). Galili U. Interaction of the natural anti-Gal antibody with alpha-galactosyl epitopes: a major obstacle for xenotransplantation in humans. Immunol Today. 1993; 14:480–2.

5). Schuurman HJ, Cheng J, Lam T. Pathology of xenograft rejection: a commentary. Xenotransplantation. 2003; 10:293–9.

6). Schuurman HJ, Pino-Chavez G, Phillips MJ, Thomas L, White DJ, Cozzi E. Incidence of hyperacute rejection in pig-to-primate transplantation using organs from hDAF- transgenic donors. Transplantation. 2002; 73:1146–51.

7). Cozzi E, Bosio E, Seveso M, Vadori M, Ancona E. Xenotransplantation-current status and future perspectives. Br Med Bull. 2005; 75-76:99–114.

8). Cowan PJ. Coagulation and the xenograft endothelium. Xenotransplantation. 2007; 14:7–12.

9). Diamond LE, Quinn CM, Martin MJ, Lawson J, Platt JL, Logan JS. A human CD46 transgenic pig model system for the study of discordant xenotransplantation. Transplantation. 2001; 71:132–42.

10). Niemann H, Verhoeyen E, Wonigeit K, Lorenz R, Hecker J, Schwinzer R, et al. Cytomegalovirus early promoter induced expression of hCD59 in porcine organs provides protection against hyperacute rejection. Transplantation. 2001; 72:1898–906.

11). Lai L, Kolber-Simonds D, Park KW, Cheong HT, Greenstein JL, Im GS, et al. Production of alpha-1,3-gal-actosyltransferase knockout pigs by nuclear transfer cloning. Science. 2002; 295:1089–92.

12). Kuwaki K, Tseng YL, Dor FJ, Shimizu A, Houser SL, Sanderson TM, et al. Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med. 2005; 11:29–31.

13). Milland J, Christiansen D, Lazarus BD, Taylor SG, Xing PX, Sandrin MS. The molecular basis for galalpha(1,3)gal expression in animals with a deletion of the alpha1,3gal-actosyltransferase gene. J Immunol. 2006; 176:2448–54.

14). Cascalho M, Platt JL. The immunological barrier to xenotransplantation. Immunity. 2001; 14:437–46.

15). Ramírez P, Montoya MJ, Ríos A, García Palenciano C, Majado M, Chávez R, et al. Prevention of hyperacute rejection in a model of orthotopic liver xenotransplantation from pig to baboon using polytransgenic pig livers (CD55, CD59, and H-transferase). Transplant Proc. 2005; 37:4103–6.

16). Cozzi E, Bhatti F, Schmoeckel M, Chavez G, Smith KG, Zaidi A, et al. Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts. Transplantation. 2000; 70:15–21.

17). Chen G, Qian H, Starzl T, Sun H, Garcia B, Wang X, et al. Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys. Nat Med. 2005; 11:1295–8.

18). Davila E, Byrne GW, LaBreche PT, McGregor HC, Schwab AK, Davies WR, et al. T-cell responses during pig-to-primate xenotransplantation. Xenotransplantation. 2006; 13:31–40.

19). Yang YG, Sykes M. Xenotransplantation: current status and a perspective on the future. Nat Rev Immunol. 2007; 7:519–31.

20). Simeonovic CJ. Xenogeneic islet transplantation. Xenotransplantation. 1999; 6:1–5.

21). Cardona K, Korbutt GS, Milas Z, Lyon J, Cano J, Jiang W, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med. 2006; 12:304–6.

22). Hering BJ, Wijkstrom M, Graham ML, Hårdstedt M, Aasheim TC, Jie T, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med. 2006; 12:301–3.

23). Tseng YL, Dor FJ, Kuwaki K, Ryan D, Wood J, Denaro M, et al. Bone marrow transplantation from alpha1,3-ga-lactosyltransferase gene-knockout pigs in baboons. Xenotransplantation. 2004; 11:361–70.

24). Cosimi AB, Sachs DH. Mixed chimerism and transplantation tolerance. Transplantation. 2004; 77:943–6.

25). Yamada K, Yazawa K, Shimizu A, Iwanaga T, Hisashi Y, Nuhn M, et al. Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med. 2005; 11:32–4.

26). Itescu S, Kwiatkowski P, Artrip JH, Wang SF, Ankersmit J, Minanov OP, et al. Role of natural killer cells, macrophages, and accessory molecule interactions in the rejection of pig-to-primate xenografts beyond the hyperacute period. Hum Immunol. 1998; 59:275–86.

27). Candinas D, Belliveau S, Koyamada N, Miyatake T, Hechenleitner P, Mark W, et al. T cell independence of macrophage and natural killer cell infiltration, cytokine production, and endothelial activation during delayed xenograft rejection. Transplantation. 1996; 62:1920–7.

28). Sprangers B, Waer M, Billiau AD. Xenotransplantation: where are we in 2008? Kidney Int. 2008; 74:14–21.

29). Lilienfeld BG, Crew MD, Forte P, Baumann BC, Seebach JD. Transgenic expression of HLA-E single chain trimer protects porcine endothelial cells against human natural killer cell-mediated cytotoxicity. Xenotransplantation. 2007; 14:126–34.

30). Lin Y, Vandeputte M, Waer M. Contribution of activated macrophages to the process of delayed xenograft rejection. Transplantation. 1997; 64:1677–83.

31). Wallgren AC, Karlsson-Parra A, Korsgren O. The main infiltrating cell in xenograft rejection is a CD4+ macrophage and not a T lymphocyte. Transplantation. 1995; 60:594–601.

32). Oldenborg PA, Zheleznyak A, Fang YF, Lagenaur CF, Gresham HD, Lindberg FP. Role of CD47 as a marker of self on red blood cells. Science. 2000; 288:2051–4.

33). Ide K, Wang H, Tahara H, Liu J, Wang X, Asahara T, et al. Role for CD47-SIRPalpha signaling in xenograft rejection by macrophages. Proc Natl Acad Sci U S A. 2007; 104:5062–6.

34). Baumann BC, Stussi G, Huggel K, Rieben R, Seebach JD. Reactivity of human natural antibodies to endothelial cells from Galalpha(1,3)Gal-deficient pigs. Transplantation. 2007; 83:193–201.

35). Morozumi K, Kobayashi T, Usami T, Oikawa T, Ohtsuka Y, Kato M, et al. Significance of histochemical expression of Hanganutziu-Deicher antigens in pig, baboon and human tissues. Transplant Proc. 1999; 31:942–4.

36). Huber-Lang M, Sarma JV, Zetoune FS, Rittirsch D, Neff TA, McGuire SR, et al. Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med. 2006; 12:682–7.

37). Selander B, Mårtensson U, Weintraub A, Holmström E, Matsushita M, Thiel S, et al. Mannan-binding lectin acti-vates C3 and the alternative complement pathway with-out involvement of C2. J Clin Invest. 2006; 116:1425–34.

38). Khalpey Z, Yuen AH, Kalsi KK, Kochan Z, Karbowska J, Slominska EM, et al. Loss of ecto-5'nucleotidase from porcine endothelial cells after exposure to human blood: Implications for xenotransplantation. Biochim Biophys Acta. 2005; 1741:191–8.

39. Morrell CN, Sun H, Swaim AM, Baldwin WM 3rd. Platelets an inflammatory force in transplantation. Am J Transplant. 2007; 7:2447–54.

40). Wagner DD, Frenette PS. The vessel wall and its interactions. Blood. 2008; 111:5271–81.

41). Schulte Am Esch J 2nd, Robson SC, Knoefel WT, Hosch SB, Rogiers X. O-linked glycosylation and functional incompatibility of porcine von Willebrand factor for human platelet GPIb receptors. Xenotransplantation. 2005; 12:30–7.

42). Roussel JC, Moran CJ, Salvaris EJ, Nandurkar HH, d'Apice AJ, Cowan PJ. Pig thrombomodulin binds human thrombin but is a poor cofactor for activation of human protein C and TAFI. Am J Transplant. 2008; 8:1101–12.

43). Lin CC, Cooper DK, Dorling A. Coagulation dysregula-tion as a barrier to xenotransplantation in the primate. Transpl Immunol. 2009; 21:75–80.

44). Ezzelarab M, Cooper DK. The potential of statins in xenotransplantation. Xenotransplantation. 2007; 14:100–3.

45). Aikawa M, Rabkin E, Sugiyama S, Voglic SJ, Fukumoto Y, Furukawa Y, et al. An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro. Circulation. 2001; 103:276–83.

46). Ledoux S, Laouari D, Essig M, Runembert I, Trugnan G, Michel JB, et al. Lovastatin enhances ecto-5'-nucleoti-dase activity and cell surface expression in endothelial cells: implication of rho-family GTPases. Circ Res. 2002; 90:420–7.

47). Wilson CA. Porcine endogenous retroviruses and xenotransplantation. Cell Mol Life Sci. 2008; 65:3399–412.

48). Bartosch B, Stefanidis D, Myers R, Weiss R, Patience C, Takeuchi Y. Evidence and consequence of porcine endogenous retrovirus recombination. J Virol. 2004; 78:13880–90.

49). Scobie L, Takeuchi Y. Porcine endogenous retrovirus and other viruses in xenotransplantation. Curr Opin Organ Transplant. 2009; 14:175–9.

50). Denner J, Schuurman HJ, Patience C. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes–chapter 5: Strategies to pre-vent transmission of porcine endogenous retroviruses. Xenotransplantation. 2009; 16:239–48.

51). Mueller NJ, Barth RN, Yamamoto S, Kitamura H, Patience C, Yamada K, et al. Activation of cytomegalovirus in pig-to-primate organ xenotransplantation. J Virol. 2002; 76:4734–40.

52). Mueller NJ, Livingston C, Knosalla C, Barth RN, Yamamoto S, Gollackner B, et al. Activation of porcine cytomegalovirus, but not porcine lymphotropic herpesvirus, in pig-to-baboon xenotransplantation. J Infect Dis. 2004; 189:1628–33.

53). Sykes M, d'Apice A, Sandrin M.IXA Ethics Committee. Position paper of the Ethics Committee of the International Xenotransplantation Association. Xenotransplantation. 2003; 10:194–203.

54). Dufrane D, Gianello P. Pig islets for clinical islet xenotransplantation. Curr Opin Nephrol Hypertens. 2009; 18:495–500.

55). McKenzie IF, Koulmanda M, Mandel TE, Sandrin MS. Pig islet xenografts are susceptible to "anti-pig" but not Gal alpha(1,3)Gal antibody plus complement in Gal o/o mice. J Immunol. 1998; 161:5116–9.

56). van der Windt DJ, Bottino R, Casu A, Campanile N, Cooper DK. Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies. Xenotransplantation. 2007; 14:288–97.

57). Giovagnoli S, Luca G, Casaburi I, Blasi P, Macchiarulo G, Ricci M, et al. Long-term delivery of superoxide dis-mutase and catalase entrapped in poly(lactide-co-glycolide) microspheres: in vitro effects on isolated neonatal porcine pancreatic cell clusters. J Control Release. 2005; 107:65–77.

58). van der Windt DJ, Bottino R, Casu A, Campanile N, Smetanka C, He J, et al. Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hcd46 transgenic porcine islets. Am J Transplant. 2009; 9:2716–26.

59). Cooper DK, Casu A. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes–chapter 4: Pre-clinical efficacy and complication data required to justify a clinical trial. Xenotransplantation. 2009; 16:229–38.

60). Kim JH, Kim HI, Lee KW, Yu JE, Kim SH, Park HS, et al. Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs. Xenotransplantation. 2007; 14:60–6.

61). Kim HI, Lee SY, Jin SM, Kim KS, Yu JE, Yeom SC, et al. Parameters for successful pig islet isolation as determined using 68 specific-pathogen-free miniature pigs. Xenotransplantation. 2009; 16:11–8.

62). Sykes M. Commentary: World Health Assembly resolution 57.18 on xenotransplantation. Transplantation. 2005; 79:636–7.

Fig. 1.

Shortage of organ donor in Korea (Data from Korean Network for Organ Sharing, KONOS).

Table 1.

Replacement of donor organ shortage

Replacement	Heart	Kidney	Liver	Lung
Allograft	Applied clinically	Applied clinically	Applied clinically	Applied clinically
Artificial organ (mechanical)	Applied clinically	Under development	Applied clinically	Under development
Cell therapy	Under development	-	Under development	-
Tissue engineering	Under development	Under development	Under development	-
Artificial organ (biological)	-	Under development	-	-
Xenograft	Under development	Under development	Under development	Under development

Source: Modified from Yang YG, Sykes M. Xenotransplantation: current status and a perspective on the future. Nat Rev Immunol 2007;7:519-31. and Cascalho, M Platt JL. New technologies for organ replacement and augmentation. Mayo Clin Proc 2005;80:370-8.

Table 2.

Solutions to organ shortage

Solution	Applicable organ	Current status
Porcine xenografts	Most organs; liver needs further investigation	Preclinical; limited clinical trials for pig pancreatic islet transplantation
Mechanical devices	Most successful for cardiac failure	Bridge therapy to transplant; destination therapy for non-transplant candidates
Bio-artificial kidney	Renal tubule assist device for acute renal failure	Extracorporeal dialysis
Tissue regeneration from stem cells	All organs	Experimental and clinicaltrials for cell therapies; solid organ regeneration still in very early experimental phase

Source: Yang YG, Sykes M. Xenotransplantation: current status and a perspective on the future. Nat Rev Immunol 2007;7:519-31. p.527

Table 3.

Different approaches to overcome xenograft rejection

Intervention	Effect
Removal of anti-α Gal antibodies	Prevention of HAR
Inhibition of complement system	Prevention of HAR
CD55, CD46, and CD59 transgenic pigs	Prevention of HAR
α GalT^−/− pigs	Prevention of HAR
	Prevention of AHXR mediated by newly elicited α Gal antibodies
	Attenuated T cell responses
	Attenuated macrophage response
HLA-E transgenic pigs	Prevention of NK-mediated xenorejection
ULBP1 transgenic pigs	Prevention of NK-mediated xenorejection
huCD47 transgenic pigs	Attenuation of macrophage response
huCD39 transgenic pigs	Prevention of thrombosis
T/B-cell suppression	Attenuation of T-and B-cell responses
Mixed chimerism	T-cell tolerance
	B-cell tolerance
	Nk hyporesponsiveness
Xenothymus transplantation	T-cell tolerance

Abbreviations: AHXR, acute humoral xenograft rejection; aGalT, a1,3-galactosyltransferase; HAR, hyperacute rejection; HLA-E, human leu-kocyte antigen-E; NK, natural killer; ULBP-1, UL16 binding protein-1.

Source: Sprangers B, Waer M, Billiau AD. Xenotransplantation: where are we in 2008? Kidney Int 2008;74:14-21. p.16

Table 4.

Results of selected pig-to-non-human primate solid organ transplantation studies

	Type	Pigs	Recipient	Number	Survival (days)	Average (days)
Kidney
Cozzi E (2000)		hDAF	Cyno	9	5,6,9,18,39,50,56,56,78	39
Richards AC (2002)		hDAF	Cyno	20	Groups 1-2 (4-60)	30.5
Yamada K (2005)		GT-KO	Baboon	6	Groups 1 (4,13,31,33,56,68)	32
				5	Groups 2 (16,18,26,81,83)	26
				3	Groups 3 (20,33,34)	33
Chen G (2005)		GT-KO	Baboon	6	8,9,10,11,13,16	10.5
Liver
Ramirez P (2005)	Ortho	hDAF/CD59/H-Transferase	Baboon	5	13,18,20,21,24 hours	20 hours
Heart
Bhatti FNK (1999)	Hete	hDAF	Baboon	9	10,12,15,15,26,32,37,44,99	26
Houser SL (2004)	Hete	hDAF	Baboon	10	4-139	27
Kuwaki K (2005)	Hete	GT-KO	Baboon	8	16,23,56,59,67,78,110,179	78
McGregor (2008)	Orho	MCP	Baboon	3	34,40,57	40
Lung
Cantu E (2003)	Ortho	vWF^-/-	Baboon	3	not available	22.6
	Ortho	MCP	Baboon	3	not available	67 hours

Abbreviations: Ortho, orthotopic; Hete, heterotropic; GT-KO, α1,3Galknockout; vWF, von-Willebrent Factor; cyno, cynomolgus. Source: Modified from Ekser B, Rigotti P, Gridelli B, Cooper DK. Xenotransplantation of solid organs in the pig-to-primate model. 2009;21:87-92. P.88.

Table 5.

Isolation variables and islet characterization

Pig strain	n	Total islet yield (IEQ)	Islet yield per pancreas weight (IEQ/g)	Isolation index	ATP (pmol/IEQ)	Stimulation index (18 m/1.8 m)
ACM	9	540,325±136,127	9,589±2,823	1.04±0.31	0.81±0.39	1.90±1.25
APM	4	117,897±68,699^†	1,752±974^†	0.73±0.37	0.71±0.14	1.98±0.79
AM	13	173,026±85,140^‡	1,931±947^‡	0.62±0.33^†	0.90±0.59	1.65±0.60
YCM	6	120,551±67,233^‡	3,460±1,985^†	0.49±0.21^†	0.96±0.65	1.75±0.94

Abbreviations: ACM, SPF adult CMS miniature; APM, adult PWG miniature; AM, adult market; YCM, SPF young CMS miniature; SPF, specific pathogen-free; CMS, Chicago Medical School.

^∗ P＜0.05,

^† P＜0.01,

^‡ P＜0.001 vs. SPF adult CMS miniature pigs.

The total islet yield of the ACM pigs (540,325±136,127 IEQ) was much higher than that of the APM pigs (117,897±68,699 IEQ), AM pigs (173,026±85,140 IEQ), or YCM pigs (120,551±67,232 IEQ; Table 2). The islet yield per gram of pancreas of the ACM pigs (9,589±2,823 IEQ/g) was also significantly higher than that of the APM pigs (1,752±874 IEQ/g), AM pigs (1,931±947 IEQ/g), or YCM pigs (3,460±1,985 IEQ/g; Table 2). The isolation index of the ACM pigs was significantly higher than those of the AM or YCM pigs. However, the purity of the islets, as estimated by dithizone staining, was not significantly different among the experimental groups and was always more than 90%.

Source: Kim JH, Kim HI, Lee KW, Yu JE, Kim SH, Park HS, et al. Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs. Xenotransplantation 2007;14:60-6. p.63

Table 6.

Predictors of high islet isolation yield

	Odds ratio	95% Confidence interval	P-value
Parameters for higher IEQ/g
Distension (moderate vs. poor)	40.06	3.21∼500.36	0.004^†
Distension (good vs. poor)	18.71	1.99∼176.17	0.010∗
Male	5.35	1.49∼19.12	0.010∗
Parameters for higher
Total IEQ
Older age group (＞2 yr)	25.60	2.22∼294.73	0.009^†
Distension (moderate vs. poor)	70.15	2.51∼1958.62	0.012^†
Male	7.55	1.35∼42.31	0.022∗
Good decapsulation	10.18	0.78∼132.79	0.077
Distension (good vs. poor)	14.05	0.73∼270.26	0.080

Binary logistic regression analysis;

^∗ P＜0.05,

^† P＜0.01.

Three donor parameters including pig body weight, age and sex, and three procurement parameters including anesthesia duration, decapsulation, and distension status were analyzed using total IEQ and IEQ/g as outcome variables Working forward analysis provided a simplified model for predicting higher islet yield. Identified variables allowed for an accuracy of 71.2% for higher

IEQ/g and 83.1% for higher total IEQ.

Source: Kim HI, Lee SY, Jin SM, Kim KS, Yu JE, Yeom SC, et al. Parameters for successful pig islet isolation as determined using 68 specific-pathogen-free miniature pigs. Xenotransplantation 2009;16:11-18. P.15.

TOOLS

Similar articles