Evaluation of growth potential of ice-free vitrified heart valves in a pediatric porcine model.

评估小儿猪模型中无冰玻璃化心脏瓣膜的生长潜力。

• 批准号: 10818132
• 负责人: Taufiek Konrad Rajab
• 金额: $ 15.88万
• 依托单位: TISSUE TESTING TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10818132
• 关键词: Administrative Supplement; Adult; Apoptosis Inhibitor; Autopsy; Biological Process; Blood Group Antigens; Businesses; Cardiovascular system; Cause of Death; Child; Childhood; Clinical; Congenital Heart Defects; Cryopreservation; Data; Development; Diagnostic; Dissection; Entrepreneurship; Evaluation; Family suidae; Freezing; Functional disorder; Future; Geography; Grant; Growth; HLA Antigens; Heart; Heart Transplantation; Heart Valves; Human; Ice; Implant; In Vitro; Individual; Inhibition of Apoptosis; Ischemia; Learning; Licensing; Lung; Market Research; Medical center; Methods; Organ; Patients; Pediatrics; Phase; Postdoctoral Fellow; Preparation; Protocols documentation; Refrigeration; Research Personnel; Risk; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Technology; Temperature; Time; Tissue Banks; Tissues; Training; Translations; Transplantation; Travel; Work; clinical application; commercialization; cryogenics; heart valve replacement; hemodynamics; immunosuppressed; in vivo; infant death; mortality; nanowarming; neonatal death; novel strategies; porcine model; post-transplant; preservation; response; tool; transplant model

Abstract: This diversity administrative supplement proposal is focused on obtaining postdoctoral support for an outstanding individual, Dr. Kamala Sundararaj, to work on our Phase I STTR grant directed at translation of ice-free cryopreservation of heart valves for pediatrics and be trained in small business entrepreneurship. Heart valve replacement in children is a serious problem because there are no heart valve implants that grow with the patient. The valves that are currently employed need to be changed as the patient grows with a very high associated mortality rate (~40%). In response to this clinical need, we are pioneering an entirely new approach to deliver growing heart valve implants, which we are calling partial heart transplantation (PHT). PHT differs from heart transplantation because only the part of the heart containing a valve is transplanted. Based on our preliminary data in immunosuppressed piglets, we recently performed the world’s first human partial heart transplant on 4/22/2022 with demonstrated valve growth. However, the chance of a donor partial heart transplant being available at just the right time is low. Therefore, we propose development of a network of tissue banks with technology licenses at major pediatric cardiovascular medical centers nationwide in preparation for clinical application. Our central hypothesis is that vitrified and nanowarmed PHTs can fulfill both their hemodynamic and biological functions after orthotopic transplantation in growing children. In this Phase I proposal there are three specific aims: First we propose optimization of short-term preservation protocols. Our working hypothesis for this aim is that PHTs will tolerate longer post-mortem cold ischemic times than intact hearts. The impact of procurement and refrigeration on piglet-derived PHTs will be evaluated by assessment of viability in vitro. This will establish the anticipated geographic range for PHT procurement after dissection based upon estimated refrigerated travel time. In the second specific aim we will optimize vitrification protocols for PHTs. Our working hypothesis for this aim is that ice-free cryo-preservation employing tissue vitrification, rapid nanowarming and apoptosis inhibition developed for adult porcine pulmonary heart valves can be further optimized for smaller PHTs required for pediatric cases. Different cryoprotectant loading times, exposure conditions, and apoptosis inhibitors will be evaluated by assessment of viability in vitro. This will establish the optimal vitrification protocol for pediatric PHTs. In the final aim we will evaluate post-transplant growth, leaflet viability and hemodynamic function of optimally vitrified and nanowarmed cryopreserved PHTs. Our working hypothesis for this aim is that optimized protocols will allow vitrified PHTs that were banked for one month to function in vivo like fresh PHTs. The optimized protocols developed in the earlier aims will be evaluated in a swine leukocyte antigen matched growing immunosuppressed piglet PHT model by transplantation. This will establish the PHT vitrification, warming, and banking methods for future clinical application. At the conclusion of these aims it is anticipated that Dr. Sundaraj will have the necessary tools to establish herself as a successful independent investigator and become an entrepreneur.

摘要：本多样性行政补充提案的重点是获得博士后的支持

项目成果

A proposed objective scale for extracorporeal membrane oxygenation circuit thrombosis.

提出的体外膜氧合回路血栓形成客观量表。

• DOI: 10.1111/ctr.15118
• 发表时间: 2023
• 期刊: Clinical transplantation
• 影响因子: 2.1
• 作者: Konsek,Haley;Mealer,Corey;Skidmore,Savannah;Collins,Monika;Tchantchaleishvili,Vakhtang;Rajab,TaufiekKonrad
• 通讯作者: Rajab,TaufiekKonrad

Morbidity and Mortality of Heterotopic Partial Heart Transplantation in Rodent Models.

啮齿动物模型异位部分心脏移植的发病率和死亡率

• DOI: 10.3390/jcdd10060234
• 发表时间: 2023-05-26
• 期刊: Journal of cardiovascular development and disease
• 影响因子: 2.4

Donor supply for partial heart transplantation in the United States.

美国部分心脏移植的供体供应。

• DOI: 10.1111/ctr.15060
• 发表时间: 2023
• 期刊: Clinical transplantation
• 影响因子: 2.1
• 作者: Quintao,Ritchelli;Kwon,JennieH;Bishara,Katherine;Rajab,TaufiekKonrad
• 通讯作者: Rajab,TaufiekKonrad

Partial heart transplantation of atrioventricular valves in complete atrioventricular septal defect-simulation of techniques using silicone-molded heart models.

• DOI: 10.1016/j.xjtc.2023.09.028
• 发表时间: 2023-12
• 期刊: JTCVS TECHNIQUES
• 影响因子: 1.6
• 作者: Hussein, Nabil;Turek, Joseph W.;Rajab, Taufiek Konrad
• 通讯作者: Rajab, Taufiek Konrad

Semilunar valve growth and function 10 years after infant heart transplantation: Predicting long-term outcomes of partial heart transplants.

婴儿心脏移植后 10 年半月瓣的生长和功能：预测部分心脏移植的长期结果。

• DOI: 10.1111/petr.14746
• 发表时间: 2024
• 期刊: Pediatric transplantation
• 影响因子: 1.3
• 作者: Rajab,TaufiekK;Abdelrahman,Mohamed;Schwartzenburg,ElridgeJ;Aykut,Berk;Turek,JosephW;McVadon,DeaniH
• 通讯作者: McVadon,DeaniH