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Islet Transplantation

CellTrans researchers have been involved in diabetes research for over 20 years, focusing on human islet isolation and transplantation. Our main contributions are: (i) improved human islet isolation efficiency and islet quality through glutamine administration to reduce oxidative injury of pancreas and application of novel hemoglobin-based O2 carrier in the isolation process. We also developed a novel islet purification method which significantly increased islet purity and quality; (ii) Clinically, we demonstrated that the UIC protocol required fewer islets per kilogram of patient body weight to achieve insulin-independence rate and better long-term graft function (60% insulin-independence post-five years) compared to the standard Edmonton protocol. Additionally, we demonstrated that islet transplantation has the potential to ameliorate diabetes-related vascular complications through improved glycemic control. In multi-institutional collaborations, our team has also contributed to translating biomaterial and stem-cell research findings into preclinical animal models.

Intra-ductal glutamine administration reduces oxidative injury during human pancreatic isolation Avila J, Barbaro B, Gangemi A, Romagnoli T, Kuechle J, Hansen M, Shapiro J, Testa G, Sankary H, Benedetti E, Lakey J, Oberholzer J. 2005. Am J Transplant. 5(12):2380-2837. PMID: 16302995.

Islet transplantation for brittle type 1 diabetes: the UIC protocol  Gangemi A, Salehi P, Hatipoglu B, Martellotto J, Barbaro B, Kuechle JB, Qi M, Wang Y, Pallan P, Owens C, Bui J, West D, Kaplan B, Benedetti E, Oberholzer J. 2008.  Am J Transplant. 8(6):1250-1261. PMID: 18444920.

Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience  Qi M, Kinzer K, Danielson KK, Martellotto J, Barbaro B, Wang Y, Bui JT, Gaba RC, Knuttinen G, Garcia-Roca R, Tzvetanov I, Heitman A, Davis M, McGarrigle JJ, Benedetti E, Oberholzer JActa Diabetol. 2014 Jul 18. PMID: 25034311.

Over ten-year insulin independence following single allogeneic islet transplant without T-cell depleting antibody induction. Williams J, Jacus N, Kavalackal K, Danielson KK, Monson RS, Wang YOberholzer J. Islets. 2018;10(4):168-174. doi: 10.1080/19382014.2018.1451281. Epub 2018 Jul 19. PMID: 30024826

Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia. Foster ED1, Bridges ND2, Feurer ID3, Eggerman TL4, Hunsicker LG5, Alejandro R6; Clinical Islet Transplantation Consortium. Diabetes Care. 2018 May;41(5):1001-1008. doi: 10.2337/dc17-1779. Epub 2018 Mar 21.

Purified Human Pancreatic Islets, CIT Culture Media with Lisofylline or Exenatide. NIH CIT Consortium Chemistry Manufacturing Controls Monitoring Committee, Ansite J, Balamurugan AN, Barbaro B, Battle J, Brandhorst D, Cano J, Chen X, Deng S, Feddersen D, Friberg A, Gilmore T, Goldstein JS, Holbrook E, Khan A, Kin T, Lei J, Linetsky E, Liu C, Luo X, McElvaney K, Min Z, Moreno J, O’Gorman D, Papas KK, Putz G, Ricordi C, Szot G, Templeton T, Wang L, Wilhelm JJ, Willits J, Wilson T, Zhang X; NIH CIT Consortium, Avila J, Begley B, Cano J, Carpentier S, Holbrook E, Hutchinson J, Larsen CP, Moreno J, Sears M, Turgeon NA, Webster D, Deng S, Lei J, Markmann JF, Bridges ND, Czarniecki CW, Goldstein JS, Putz G, Templeton T, Wilson T, Eggerman TL, Al-Saden P, Battle J, Chen X, Hecyk A, Kissler H, Luo X, Molitch M, Monson N, Stuart E, Wallia A, Wang L, Wang S, Zhang X, Bigam D, Campbell P, Dinyari P6 Kin T6 Kneteman N6 Lyon J, Malcolm A, O’Gorman D, Onderka C, Owen R, Pawlick R, Richer B, Rosichuk S, Sarman D, Schroeder A, Senior PA, Shapiro AMJ, Toth L, Toth V, Zhai W, Johnson K, McElroy J, Posselt AM, Ramos M, Rojas T, Stock PG, Szot G, Barbaro B, Martellotto J, Oberholzer J, Qi M, Wang Y, Bayman L, Chaloner K, Clarke W, Dillon JS, Diltz C, Doelle GC, Ecklund D, Feddersen D, Foster E, Hunsicker LG, Jasperson C, Lafontant DE, McElvaney K, Neill-Hudson T, Nollen D, Qidwai J, Riss H, Schwieger T, Willits J, Yankey J, Alejandro R, Corrales AC, Faradji R, Froud T, Garcia AA, Herrada E, Ichii H, Inverardi L, Kenyon N, Khan A, Linetsky E, Montelongo J, Peixoto E, Peterson K, Ricordi C, Szust J, Wang X, Abdulla MH, Ansite J, Balamurugan AN, Bellin MD, Brandenburg M, Gilmore T, Harmon JV, Hering BJ, Kandaswamy R, Loganathan G, Mueller K, Papas KK, Pedersen J, Wilhelm JJ, Witson J, Dalton-Bakes C, Fu H, Kamoun M, Kearns J, Li Y, Liu C, Luning-Prak E, Luo Y, Markmann E, Min Z, Naji A, Palanjian M, Rickels M, Shlansky-Goldberg R, Vivek K, Ziaie AS, Fernandez L, Kaufman DB, Zitur L, Brandhorst D, Friberg A, Korsgren O. CellR4 Repair Replace Regen Reprogram. 2017;5(3). pii: e2377. Epub 2017 May 26.

Effect of Manufacturing Procedures on Human Islet Isolation From Donor Pancreata Standardized by the North American Islet Donor Score. Yeh CC, Wang LJ, McGarrigle JJ, Wang Y, Liao CC, Omami M, Khan A, Nourmohammadzadeh M, Mendoza-Elias J, McCracken B, Marchese E, Barbaro B, Oberholzer J. Cell Transplant. 2017 Jan 24;26(1):33-44. doi: 10.3727/096368916X692834. Epub 2016 Aug 12. PMID: 27524672.

National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities. Ricordi C, Goldstein JS, Balamurugan AN, Szot GL, Kin T, Liu C, Czarniecki CW, Barbaro B, Bridges ND, Cano J, Clarke W, Eggerman TL, Hunsicker LG, Kaufman DB, Khan A, Lafontant DE, Linetsky E, Luo X, Markmann JF, Naji A, Korsgren O, Oberholzer J, Turgeon NA, Brandhorst D, Chen X, Friberg AS, Lei J, Wang LJ, Wilhelm JJ, Willits J, Zhang X, Hering BJ, Posselt AM, Stock PG, Shapiro AM, Chen X. Diabetes. 2016 Nov;65(11):3418-3428. Epub 2016 Jul 27.

A Multicenter Study: North American Islet Donor Score in Donor Pancreas Selection for Human Islet Isolation for Transplantation. Wang LJ, Kin T, O’Gorman D, Shapiro AMJ, Naziruddin B, Takita M, Levy MF, Posselt AM, Szot GL, Savari O, Barbaro B, McGarrigle J, Yeh CC, Oberholzer J, Lei J, Chen T, Lian M, Markmann JF, Alvarez A, Linetsky E, Ricordi C, Balamurugan AN, Loganathan G, Wilhelm JJ, Hering BJ, Bottino R, Trucco M, Liu C, Min Z, Li Y, Naji A, Fernandez LA, Ziemelis M, Danobeitia JS, Millis JM, Witkowski P. Cell Transplant. 2016;25(8):1515-1523. doi: 10.3727/096368916X691141. Epub 2016 Feb 26.

Systematic analysis of donor and isolation factor’s impact on human islet yield and size distribution. Wang Y, Danielson KK, Ropski A, Harvat T, Barbaro B, Paushter D, Qi M, Oberholzer J. Cell Transplant. 2013;22(12):2323-33. doi: 10.3727/096368912X662417. Epub 2013 Jan 28.

Histidine-tryptophan-ketoglutarate and University of Wisconsin solution demonstrate equal effectiveness in the preservation of human pancreata intended for islet isolation: a large-scale, single-center experience. Paushter DH, Qi M, Danielson KK, Harvat TA, Kinzer K, Barbaro B, Patel S, Hassan SZ, Oberholzer J, Wang Y. Cell Transplant. 2013;22(7):1113-21. doi: 10.3727/096368912X657332. Epub 2012 Oct 2.

Long-term metabolic and immunological follow-up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts: four cases. Basta G, Montanucci P, Luca G, Boselli C, Noya G, Barbaro B, Qi M, Kinzer KP, Oberholzer J, Calafiore R. Diabetes Care. 2011 Nov;34(11):2406-9. doi: 10.2337/dc11-0731. Epub 2011 Sep 16.

Highly purified versus filtered crude collagenase: comparable human islet isolation outcomes. Wang Y, Paushter D, Wang S, Barbaro B, Harvat T, Danielson KK, Kinzer K, Zhang L, Qi M, Oberholzer J. Cell Transplant. 2011;20(11-12):1817-25. doi: 10.3727/096368911X564994. Epub 2011 Mar 7.

Comparing cooling systems for the COBE 2991 cell separator used in the purification of human pancreatic islets of Langerhans. Adewola A, Mage R, Hansen M, Barbaro B, Mendoza-Elias J, Harvat T, Morel PH, Oberholzer J, Wang Y. Cryo Letters. 2010 Jul-Aug;31(4):310-7.

Human pancreatic islet isolation: Part I: digestion and collection of pancreatic tissue. Qi M, Barbaro B, Wang S, Wang Y, Hansen M, Oberholzer J. J Vis Exp. 2009 May 26;(27). pii: 1125. doi: 10.3791/1125.

Human pancreatic islet isolation: Part II: purification and culture of human islets. Qi M, Barbaro B, Wang S, Wang Y, Hansen M, Oberholzer J. J Vis Exp. 2009 May 26;(27). pii: 1343. doi: 10.3791/1343.

Increased albumin concentration reduces apoptosis and improves functionality of human islets. Barbaro B, Kuechle J, Salehi P, Rodriguez L, Qi M, Gangemi A, Benedetti E, Oberholzer J. Artif Cells Blood Substit Immobil Biotechnol. 2008;36(1):74-81. doi: 10.1080/10731190701857819.

Improved human pancreatic islet purification with the refined UIC-UB density gradient. Barbaro B, Salehi P, Wang Y, Qi M, Gangemi A, Kuechle J, Hansen MA, Romagnoli T, Avila J, Benedetti E, Mage R, Oberholzer J. Transplantation. 2007 Nov 15;84(9):1200-3.

Improved outcomes in islet isolation and transplantation by the use of a novel hemoglobin-based O2 carrier. Avila JG, Wang Y, Barbaro B, Gangemi A, Qi M, Kuechle J, Doubleday N, Doubleday M, Churchill T, Salehi P, Shapiro J, Philipson LH, Benedetti E, Lakey JR, Oberholzer J. Am J Transplant. 2006 Dec;6(12):2861-70.

Human islet isolation outcomes from pancreata preserved with Histidine-Tryptophan Ketoglutarate versus University of Wisconsin solution. Salehi P, Hansen MA, Avila JG, Barbaro B, Gangemi A, Romagnoli T, Wang Y, Qi M, Murdock P, Benedetti E, Oberholzer J. Transplantation. 2006 Oct 15;82(7):983-5. PMID: 17038916 DOI: 10.1097/

Intra-ductal glutamine administration reduces oxidative injury during human pancreatic islet isolation. Avila J, Barbaro B, Gangemi A, Romagnoli T, Kuechle J, Hansen M, Shapiro J, Testa G, Sankary H, Benedetti E, Lakey J, Oberholzer J. Am J Transplant. 2005 Dec;5(12):2830-7. PMID: 16302995 DOI: 10.1111/j.1600-6143.2005.01109.x