Team Member

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Co-Founder & CSO, XOSTem Biosciences, Ltd.

Jonathan R.T. Lakey, PhD is a co-founder of XOStem, Chief Scientific Officer and Chair of the Scientific Advisory Board. For more than two decades, he has been a global research leader in the fields of diabetes, islet and stem cell transplantation, exosomes, cellular metabolism and signaling, immunology, cellular encapsulation, in vivo biomaterial and bio-implantable polymers. His work and discoveries are seminal  contributions to the diabetes transplant technology and platform.

Dr. Lakey is Emeritus Professor in the Department of Surgery and in Biomedical Engineering at the University of California Irvine. Dr. Lakey also served as the Director of the Clinical Islet Program at the University of California Irvine. Prior to joining UC Irvine Dr Lakey was at University of Alberta where together with Dr. James Shapiro developed the ‘Edmonton Protocol” for the treatment of diabetes. Dr. Lakey is widely sought after as a speaker in the field of diabetes, islet transplantation, and regulatory standards of cell and tissue transplantation. He is widely published with over 495 scientific papers, 45 book chapters, and 500 scientific abstracts. He recently published a technical book on islet isolation. Dr. Lakey sits on the editorial boards of several diabetes and  transplantation journals, serving as reviewer for multiple journals, and has served as a Counselor for the Cell Transplant Society.

Selected References

Published Articles

Hu S, Kuwabara R, Navarro Chica CE, Smink AM, Koster T, Medina JD, de Haan BJ, Beukema M, Lakey JRT, García AJ, de Vos P. Toll-like receptor 2-modulating pectin-polymers in alginate-based microcapsules attenuate immune responses and support islet-xenograft survival. Biomaterials. 2021 Jan;266:120460. doi: 10.1016/j.biomaterials.2020.120460. Epub 2020 Oct 19. PMID: 33099059. https://pubmed.ncbi.nlm.nih.gov/33099059/

Kuwabara R, Hu S, Smink AM, Orive G, Lakey JRT, de Vos P. Applying Immunomodulation to Promote Longevity of Immunoisolated Pancreatic Islet Grafts. Tissue Eng Part B Rev. 2021 Feb 24. doi: 10.1089/ten.TEB.2020.0326. Epub ahead of print. PMID: 33397201. https://pubmed.ncbi.nlm.nih.gov/33397201/

Whaley D, Damyar K, Witek RP, Mendoza A, Alexander M, Lakey JR. Cryopreservation: An Overview of Principles and Cell-Specific Considerations. Cell Transplant. 2021 Jan-Dec;30:963689721999617. doi: 10.1177/0963689721999617. PMID: 33757335; PMCID: PMC7995302. https://pubmed.ncbi.nlm.nih.gov/33757335/

Mohammadi MR, Rodriguez SM, Luong JC, Li S, Cao R, Alshetaiwi H, Lau H, Davtyan H, Jones MB, Jafari M, Kessenbrock K, Villalta SA, de Vos P, Zhao W, Lakey JRT. Exosome loaded immunomodulatory biomaterials alleviate local immune response in immunocompetent diabetic mice post islet xenotransplantation. Commun Biol. 2021 Jun 3;4(1):685. doi: 10.1038/s42003-021-02229-4. PMID: 34083739; PMCID: PMC8175379. https://pubmed.ncbi.nlm.nih.gov/34083739/

Mohammadi M, Luong JC, Rodriguez SM, Cao R, Wheeler AE, Lau H, Li S, Shabestari SK, Chadarevian JP, Alexander M, de Vos P, Zhao W, Lakey JRT. Controlled Release of Stem Cell Secretome Attenuates Inflammatory Response against Implanted Biomaterials. Adv Healthc Mater. 2020 Jun;9(12):e1901874. doi: 10.1002/adhm.201901874. Epub 2020 May 18. PMID: 32419390. https://pubmed.ncbi.nlm.nih.gov/32419390/

Medina JD, Alexander M, Hunckler MD, Fernández-Yagüe MA, Coronel MM, Smink AM, Lakey JR, de Vos P, García AJ. Functionalization of Alginate with Extracellular Matrix Peptides Enhances Viability and Function of Encapsulated Porcine Islets. Adv Healthc Mater. 2020 May;9(9):e2000102. doi: 10.1002/adhm.202000102. Epub 2020 Apr 7. PMID: 32255552; PMCID: PMC7598935.  https://pubmed.ncbi.nlm.nih.gov/32255552/

Lau H, Corrales N, Rodriguez S, Luong C, Mohammadi M, Khosrawipour V, Li S, Alexander M, de Vos P, Lakey JRT. Dose-dependent effects of necrostatin-1 supplementation to tissue culture media of young porcine islets. PLoS One. 2020 Dec 7;15(12):e0243506. doi: 10.1371/journal.pone.0243506. PMID: 33284818; PMCID: PMC7721208. https://pubmed.ncbi.nlm.nih.gov/33284818/

Lau H, Corrales N, Rodriguez S, Luong C, Zaldivar F, Alexander M, Lakey JRT. An islet maturation media to improve the development of young porcine islets during in vitro culture. Islets. 2020 May 3;12(3):41-58. doi: 10.1080/19382014.2020.1750933. Epub 2020 May 27. PMID: 32459554; PMCID: PMC7527017. https://pubmed.ncbi.nlm.nih.gov/32459554/

Corrales N, Park S, Lau H, Xu I, Luong C, Rodriguez S, Mönch J, Alexander M, Lakey JR. Comparison of Islet Characterization from Use of Standard Crude Collagenase to GMP-Grade Collagenase Enzyme Blends in Preweaned Porcine Islet Isolations. Cell Transplant. 2020 Jan-Dec;29:963689720977835. doi: 10.1177/0963689720977835. PMID: 33267618; PMCID: PMC7873766. https://pubmed.ncbi.nlm.nih.gov/33267618/

Cao R, Avgoustiniatos E, Papas K, de Vos P, Lakey JRT. Mathematical predictions of oxygen availability in micro- and macro-encapsulated human and porcine pancreatic islets. J Biomed Mater Res B Appl Biomater. 2020 Feb;108(2):343-352. doi: 10.1002/jbm.b.34393. Epub 2019 Apr 23. PMID: 31013399. https://pubmed.ncbi.nlm.nih.gov/31013399/

Riazifar M, Mohammadi MR, Pone EJ, Yeri A, Lässer C, Segaliny AI, McIntyre LL, Shelke GV, Hutchins E, Hamamoto A, Calle EN, Crescitelli R, Liao W, Pham V, Yin Y, Jayaraman J, Lakey JRT, Walsh CM, Van Keuren-Jensen K, Lotvall J, Zhao W. Stem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders. ACS Nano. 2019 Jun 25;13(6):6670-6688. doi: 10.1021/acsnano.9b01004. Epub 2019 May 29. PMID: 31117376; PMCID: PMC6880946. https://pubmed.ncbi.nlm.nih.gov/31117376/

Stiner R, Alexander M, Liu G, Liao W, Liu Y, Yu J, Pone EJ, Zhao W, Lakey JRT. Transplantation of stem cells from umbilical cord blood as therapy for type I diabetes. Cell Tissue Res. 2019 Nov;378(2):155-162. doi: 10.1007/s00441-019-03046-2. Epub 2019 Jun 17. PMID: 31209568.  https://pubmed.ncbi.nlm.nih.gov/31209568/

Smink AM, de Haan BJ, Lakey JRT, de Vos P. Polymer scaffolds for pancreatic islet transplantation - Progress and challenges. Am J Transplant. 2018 Sep;18(9):2113-2119. doi: 10.1111/ajt.14942. Epub 2018 Jun 13. PMID: 29790274. https://pubmed.ncbi.nlm.nih.gov/29790274/

Kojayan GG, Alexander M, Imagawa DK, Lakey JRT. Systematic review of islet cryopreservation. Islets. 2018 Jan 2;10(1):40-49. doi: 10.1080/19382014.2017.1405202. Epub 2018 Jan 9. PMID: 29315020; PMCID: PMC5800373. https://pubmed.ncbi.nlm.nih.gov/29315020/

Kopan C, Tucker T, Alexander M, Mohammadi MR, Pone EJ, Lakey JRT. Approaches in Immunotherapy, Regenerative Medicine, and Bioengineering for Type 1 Diabetes. Front Immunol. 2018 Jun 12;9:1354. doi: 10.3389/fimmu.2018.01354. PMID: 29963051; PMCID: PMC6011033. https://pubmed.ncbi.nlm.nih.gov/29963051/

Krishnan R, Ko D, Foster CE 3rd, Liu W, Smink AM, de Haan B, De Vos P, Lakey JR. Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials. Methods Mol Biol. 2017;1479:305-333. doi: 10.1007/978-1-4939-6364-5_24. PMID: 27738946. https://pubmed.ncbi.nlm.nih.gov/27738946/

Smink AM, Li S, Hertsig DT, de Haan BJ, Schwab L, van Apeldoorn AA, de Koning E, Faas MM, Lakey JR, de Vos P. The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets. Transplantation. 2017 Apr;101(4):e112-e119. doi: 10.1097/TP.0000000000001663. PMID: 28207637; PMCID: PMC7228571. https://pubmed.ncbi.nlm.nih.gov/28207637/

Krishnan R, Buder B, Alexander M, Foster CE 3rd, Lakey JR. Juvenile porcine islets can restore euglycemia in diabetic athymic nude mice after xenotransplantation. Transplantation. 99(4):710-6, 2015. https://pubmed.ncbi.nlm.nih.gov/25793438/

Buder B, Alexander M, Krishnan R, Chapman DW, Lakey JRT. Encapsulated Islet Transplantation: Strategies and Clinical Trials. Immune Network 13(6):235-239, 2013. https://pubmed.ncbi.nlm.nih.gov/24385941/

Robles L, Storrs R, Lamb M, Alexander M, Lakey JRT. Current status of islet encapsulation. Cell Transplantation. 23 (); 2014. https://pubmed.ncbi.nlm.nih.gov/23880554/

Miranda P, Mohan V, Ganthimathy S, Anjana R, Gunasekaran S, Thiagarajan V, Churchill A, Kin T, Shapiro A, Lakey JRT. Human Islet Mass, Morphology, and survival after cryopreservation using the Edmonton protocol. Landes Bioscience, 2013. https://pubmed.ncbi.nlm.nih.gov/24759005/

Ader M, Storrs R, Endres J, Lamb M, Paredes EM, Bergman RN, Lakey JRT. Testing in vivo functionality of alginate-encapsulated pancreatic islets: advancing to the surgically-induced diabetic canine model. Diabetologia, 55:(S1);439, 2012.

Lamb M, Storrs R, Li S, Alexander M, Liang O, Laugenour K, Dorian R, Chapman D, Ichii H, Imagawa D, Foster C, King S, Lakey JRT. Function and Viability of Human Islets Encapsulated in Alginate Sheets: In Vitro and In Vivo Culture. Elsevier, Transplantation Proceedings, 43, 3265-3266, 2011. https://pubmed.ncbi.nlm.nih.gov/22099772/

Kin, T, O’Neil, J, Pawlick, R, Korbutt, G, Shapiro, AMJ, Lakey, JRT. The Use of an Approved Biodegradable Polymer Scaffold as a Solid Support System for Improvement of Islet Engraftment. Artificial Organs, 32(12): 990-993, 2008. https://pubmed.ncbi.nlm.nih.gov/19133030/

Lakey JRT, Kin T, Warnock GL, Shapiro AMJ, Tsapongas P, Imes S, Korbutt GS, Kneteman NM, Rajotte RV, Ryan EA. Long-Term Graft Function After Allogeneic Islet Transplantation. Cell Transplant;16(4):441-446, 2007. https://pubmed.ncbi.nlm.nih.gov/28858603/

Shapiro, AM, Ricordi, C, Hering, BJ, Auchincloss, H, Lindblad, R, Robertson, P, Secchi, A, Brendal, MD, Berney, T, Brennan, DC, Cagliero, E, Alejandro, R, Ryan, E, DiMercurio, B, MNorel, P, Polonsky, KS, Reems, JA, Bretzel, RG, Bertuzzi, F, Froud, T, Kandaswamy, R, Sutherland, DE, Eisenbarth, G, Segal, M, Preiksaitis, J, Korbutt, G, Barton, FB, Viviano, L, Seyfert-Margolis, V, Bluestone, J, Lakey, JRT. International Trial of the Edmonton Protocol for islet transplantation. New England J Medicine. 355(13) 1318-1330, Sep 2006 https://pubmed.ncbi.nlm.nih.gov/17005949/

Miszta-Lane H, Mirbolooki M, Shapiro AMJ, Lakey JRT. Stem Cell Sources for Clinical Islet Transplantation in Type 1 Diabetes: Embryonic or Adult Stem Cells. Medical Hypotheses 67(4):909-913. Epub, Jun 2006  https://pubmed.ncbi.nlm.nih.gov/16762516/

Mirbolooki M, Shapiro AMJ, Lakey JRT. A Perspective on Clinical Islet Transplantation: Past, Present, and Developments for Future. Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents 6(2):191-208, 2006  https://pubmed.ncbi.nlm.nih.gov/26556410/

Lakey JRT, Mirbolooki M, Shapiro AMJ. Current Status of Islet Transplantation. Methods in Molecular Biology. 333: 47-104, Mar 2006  https://pubmed.ncbi.nlm.nih.gov/16790847/

Ryan E, Paty B, Senior P, Bigam D, Alfadhli E, Kneteman N, Lakey JRT, Shapiro A. Five-year follow-up after clinical islet transplantation Diabetes 54(7):2060-9, Jul 2005 https://pubmed.ncbi.nlm.nih.gov/15983207/

Shapiro AMJ, Lakey JRT, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.New England J. of Medicine 343:230 238, 2000 https://pubmed.ncbi.nlm.nih.gov/10911004/

Book Chapters

Kneteman NM, Lakey JRT, Warnock GL, et al: Pancreas procurement and preservation: impact on islet recovery and viability. In: Ricordi C, ed. Pancreatic Islet Cell Transplantation. Austin, TX: R.G. Landes, pp 72-79, 1992

Warnock GL, Ziliang A, Lakey JRT, Rajotte RV: Islet isolation from canine pancreas. In:Lanza RP, Chick WL, eds. Pancreatic Islet Transplantation Volume 1: Procurement of
Pancreatic Islets. Austin, TX: R.G. Landes, pp 81-95, 1994

Rajotte RV, Lakey JRT, Warnock GL: Islet cryopreservation. In: Lanza RP, Chick WL, eds. Pancreatic Islet Transplantation Volume 1: Procurement of Pancreatic
Islets.
Austin, TX: R.G. Landes, pp 137-147, 1994

Lakey JRT, Rajotte RV, Warnock GL: Quality control issues for the maintenance of
sterility in the human islet isolation laboratory.
Section G: Pancreatic Islets. In: Ricordi C, ed. Methods in Cell Transplantation. Austin, TX: R.G. Landes, pp 411-419,1995

Lakey JRT, Rajotte RV, Warnock GL, Kneteman NM: Pancreas procurement for islet isolation and pancreas storage prior to islet isolation. Section G: Pancreatic Islets. In: Ricordi C, ed. Methods in Cell Transplantation. Austin, TX: R.G. Landes, pp 421-431, 1995

Rajotte RV, Lakey JRT, Warnock: Adult islet cryopreservation. Section G: Pancreatic Islets. In: Ricordi C, ed. Methods in Cell Transplantation. Austin, TX: R.G. Landes, pp 517-524, 1995

Rajotte RV, Warnock GL, Lakey JRT: Islet cryopreservation protocols. Chick WL, Lanza RP, Eds. Medical Intelligence Unit: Pancreatic Islet Transplantation Series. RG Landes Company, Austin, 1996

Shapiro AMJ, Ryan EA and Lakey JRT: Pancreatic Islet Transplantation in the Treatment of Diabetes Mellitus. Book chapter in ‘Clinical Endocrinology and Metabolism’. Special Issue on Endocrine Surgery. Guest Editor JR Farndon. Baillière’s Best Practice and Research, Editor, Jeff MP Holly. Vol 15(2):241-264, Jun 2001

Shapiro AMJ, Ryan EA, Paty BW, Lakey JRT: Pancreas and islet transplantation. In: John Pickup J , Williams G, eds. Textbook of Diabetes, 3rd Edition. Blackwell Science, April 2002

Oberholzer J, Shapiro AMJ, Lakey JRT, Ryan EA, Rajotte RV, Korbutt GS, Morel P: Current status of islet cell transplantation. In: Cameron JL, Evers BM, et al. Advances in Surgery, Vol 37, Mosby, pp 253-282, 2003

Norrie B, Jalil A, Lakey JRT, Rajotte RV, Uludag H: In-situ crosslinking thermoreversible polymers for cell entrapment. In: Hasicri N, Hasicri V, eds. Biomaterials From Molecules to Engineered Tissues, Kluwer Academic/Plenum Publishers, pp 19-28, 2004

Ryan EA, Lakey JRT, Paty BW, Shapiro AMJ: Islet transplantation. In DeFronzo RA, Ferrannini E, Keen h, Zimmet P. International Textbook of Diabetes Mellitus, 3rd Edition. John Wiley & Sons, Ltd, pp 1067-1078, 2004

Paty BW, Ryan EA, Lakey JRT, Shapiro AMJ: Islet Transplantation. In: LeRoith D, Taylor SI, Olefsky JM, eds. Diabetes Mellitus: A Fundamental and Clinical Text, Third Edition. Lippincott Williams & Wilkins, pp 721-732, 2004

Shapiro AMJ, Ryan EA, Lakey JRT: Islet Transplantation in the Treatment of Diabetes Mellitus. In: Best Practice and Research Compendium: Diabetes. Edited by Professor A.H. Barnett. Published by Elsevier Limited, 2005

Shapiro AMJ, Ryan EA, Lakey JRT: Islet transplantation in the treatment of diabetes. Submitted to Rapid Medical Media October, 2005

Lakey JRT, Mirbolooki M, Shapiro J: Current status of Clinical Islet cell transplantation. In: Hornick P, Rose M, eds. Transplantation Immunology, Humana Press, pp 47-103, Mar 2006

Mirbolooki M, Lakey JRT: Pancreas preservation for islet isolation. In: Shapiro AMJ, Shawn AMJ (Eds.) Islet Transplantation and Beta Cell Replacement Therapy, Informa Healthcare, NY, pp 99-114, 2007

Fisher JS, Mirbolooki MR, Lakey JRT, Robertson RP, Marsh CL: Pancreas and Islet Transplantation. In Feehally J, Floege J, Johnson RJ. Comprehensive Clinical Nephrology, 3rdEdition, Mosby/Elsevier, pp 1131-1144, 2007

Mirbolooki M, Lakey JRT, Kin T, Murdoch T, Shapiro AMJ: Aspects and changes of islet isolation. In: Shapiro AMJ, Shawn AMJ, eds. Islet Transplantation and Beta Cell Replacement Therapy. Informa Healthcare, pp 115-134, 2007

Kin, T, Mirbolooki M, Lakey JRT: Design and implementation of a cell processing facility. In: Halberstadt CR, Eerich DF, eds. Cellular Transplantation: From Laboratory to Clinic. Elsevier Inc., pp 629-634 (Chapter 33), 2007

Mirbolooki M, Lakey JRT: Pancreas preservation for islet isolation. In: Islet Transplantation and Beta Cell Replacement Therapy. Shapiro AMJ, Shawn AMJ, eds. Informa Healthcare, pp 99-114, 2007

Marsh C, Mirbolooki M, Lakey JRT, Risk factors affecting islet yield function. In: Kandeel FR, ed. Islets: Biology, Immunology, and Clinical Transplantation. Springer, 2009.

Fisher JS, Mirbolooki MR, Lakey JRT, Robertson RP, Marsh CL: Pancreas and Islet Transplantation. In Feehally J, Floege J, Johnson RJ. , Comprehensive Clinical Nephrology, Mosby/Elesvier , 2009.

Fisher JS, Mirbolooki MR, Lakey JRT, Robertson RP, Marsh CL: Pancreas and Islet Transplantation. In Feehally J, Floege J, In: Comprehensive Clinical Nephrology, 4th edition. Feehally J, Floege J, Johnson RJ (Eds). Mosby, 106:1232-1244, 2010.

Mirbolooki M, Bozorgmanesh H, Foster CE, Kuhtrieber W, Lakey JRT: Tissue and Cell Isolation. In: Comprehensive Biotechnology, 2nd edition. Moo-Young M, Butler M. (Eds.), Vol 1, Section 6; 67, 2011.

Fisher JS, Mirbolooki MR, Lakey JRT, Robertson RP, Marsh CL: Pancreas and Islet Transplantation. In Feehally J, Floege J, In: Comprehensive Clinical Nephrology, 5th edition. Feehally J, Floege J, Johnson RJ (Eds). 12:10, 2013.

Lakey, JRT, Robles L, Morgan L, Alexander M, Botvinick E, Foster, C. Islet Encapsulation. In: Islets of Langerhans, 2nd Edition. Islam, Md. Shahidul (Ed) Ch 46: 2014.

Lakey, JRT, Alexander, M, Chapman, DW, Imagawa, D, Krishnan, R. Islet Xenotransplantation: An update on recent advances and future Prospects. In: Islets of Langerhans, 2nd, Ed, Islam, Md. Shahidul (Ed), 45: 2014.

Fisher J, Lakey JRT, Marsh CL. Pancreas and Islet Transplantation, Comprehensive Clinical Nephrology, 110, 2014.

Krishnan R, Imagawa D, Foster CE III, Lakey JRT. Encapsulation Technologies in Beta Cell Replacement Therapies for Type 1 Diabetes. (In Press)

Krishnan R, Ko, D, Foster CE III, Liu, W, De Vos, P, Lakey JRT. Immunological Challenges facing Translation of Alginate Encapsulated Islet Transplantation to Human Clinical Trials. Opara, M Ed. Springer (In Press), 2015.

Krishnan R, Imagawa D, Foster CE III, Lakey JRT. Encapsulation Technologies in Beta Cell Replacement Therapies for Type 1 Diabetes, Xenotransplanation, Open Access ebook (In Press).

Krishnan, R, Alexander, M, Lakey, JRT. Islet and Stem cell Encapsulation for clinical transplantation. In Nanomaterials and Regenerastive Medicine (In Press, 2015).

Alexander M, Nguyen H, Flores A, Li S, de Vos P, Botvinick E, Lakey JRT. Avoiding Immunosuppression for Islet Transplantation – Use of Protective Biomaterials. In: Pancreas, InTech. (In Press), 2016.