Journal of Molecular and Cellular Cardiology, Год журнала: 2022, Номер 172, С. 109 - 119
Опубликована: Авг. 27, 2022
Язык: Английский
Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(28)
Опубликована: Июнь 28, 2023
Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better results. Parathyroid cells generated from pluripotent stem in vitro date cannot mimic the physiological responses extracellular calcium that essential for homeostasis. We thus hypothesized blastocyst complementation (BC) could be strategy generating PTG and compensating loss function. here describe generation fully PTGs mouse embryonic (mESCs) single-step BC. Using CRISPR-Cas9 knockout Glial missing2 (Gcm2), we efficiently produced aparathyroid embryos In these embryos, mESCs differentiated into endocrinologically mature rescued Gcm2-/- mice neonatal death. mESC-derived responded calcium, restoring homeostasis on transplantation surgically rendered hypoparathyroid. also successfully interspecies rat neonates, an accomplishment potential future human using xenogeneic animal Our results demonstrate BC can produce endocrine organs constitute concept hypoparathyroidism.
Язык: Английский
Процитировано
9
Developmental Cell, Год журнала: 2023, Номер 58(24), С. 2881 - 2895.e7
Опубликована: Ноя. 14, 2023
Generating organs from stem cells through blastocyst complementation is a promising approach to meet the clinical need for transplants. In order generate rejection-free organs, of both parenchymal and vascular must be achieved, as endothelial play key role in graft rejection. Here, we used lineage-specific cell ablation system produce mouse embryos unable form cardiac systems. By intraspecies complementation, rescued heart development separately combination, obtaining complemented hearts with cardiomyocytes exogenous origin. Complemented chimeras were viable reached adult stage, showing normal function no signs histopathological defects heart. Furthermore, implemented rat-to-mouse xenogeneic whose completely rat These results represent an advance experimentation towards vivo generation transplantable organs.
Язык: Английский
Процитировано
9
Hepatic Medicine Evidence and Research, Год журнала: 2024, Номер Volume 16, С. 11 - 29
Опубликована: Фев. 1, 2024
Orthotopic liver transplantation (OLT) currently serves as the sole definitive treatment for thousands of patients suffering from end-stage disease; and existing supply donor livers OLT is drastically outpaced by increasing demand. To alleviate this significant gap in treatment, several experimental approaches have been devised with aim either offering interim support to waiting on transplant list or bioengineering complete infusing them fresh hepatic cells. Recently, interspecies blastocyst complementation has emerged a promising method generating organs utero over short timeframe. When coupled gene editing technology, it brought about potentially revolutionary transformation regenerative medicine. Blastocyst harbors notable potential human large animals, which could be used xenotransplantation humans, addressing scarcity OLT. Nevertheless, substantial ethical challenges still need overcome produce larger domestic animals like pigs. This review compiles current understanding outlines future possibilities humans.
Язык: Английский
Процитировано
3
Disease Models & Mechanisms, Год журнала: 2023, Номер 16(5)
Опубликована: Май 1, 2023
ABSTRACT The 2-month-survival of a terminally ill patient who received genetically modified pig heart has demonstrated that cardiac xenotransplantation could provide therapeutic option for patients cannot receive human organ. Genetic engineering to overcome transplant rejection mechanisms, coagulation dysregulation and overgrowth xeno-hearts been the key this success. concept exogenesis – replacement specific cellular populations tissue structures with cells is promising extension because it further reduce immunological physiological obstacles. Additionally, in aim preventing need transplant, tailored models mimicking monogenic disorders have developed test new molecular therapies. Thus, engineered pigs powerful platform xenogeneic, exogenic endogenic restoration function.
Язык: Английский
Процитировано
7
Cell Transplantation, Год журнала: 2023, Номер 32
Опубликована: Янв. 1, 2023
Organ transplantation is a highly utilized treatment for many medical conditions, yet the number of patients waiting organs far exceeds available. The challenges and limitations currently associated with organ technological advances in gene editing techniques have led scientists to pursue alternate solutions donor shortage. Growing human animals harvesting those into humans one such solution. These chimeric usually certain genes necessary specific organ’s development inhibited at an early developmental stage, followed by addition cultured pluripotent cells fill that niche. result animal contains which are available transplant patient, circumventing some involved transplantation. In this review, we will discuss both current scientific legal landscape human–animal chimera (HAC) research. We present overview allow creation HACs, patents exist on these methods, as well public attitude understanding can influence HAC research policy. complement our discussion regulatory national state level, while also contrasting U.S. legislation regulations other countries. Overall, provide comprehensive analysis barriers conducting HACs generation transplantable organs, recommendations future.
Язык: Английский
Процитировано
7
Stem Cell Reports, Год журнала: 2022, Номер 17(9), С. 1942 - 1958
Опубликована: Авг. 4, 2022
Blastocyst complementation denotes a technique that aims to generate organs, tissues, or cell types in animal chimeras via injection of pluripotent stem cells (PSCs) into genetically compromised blastocyst-stage embryos. Here, we report on successful the male germline adult following mouse rat PSCs blastocysts carrying mutation Tsc22d3, an essential gene for spermatozoa production. Injection Tsc22d3-Knockout (KO) gave rise intraspecies exclusively embodying PSC-derived functional spermatozoa. In addition, embryonic (rESCs) Tsc22d3-KO embryos produced interspecies mouse-rat solely harboring spermatids and capable fertilizing oocytes. Furthermore, using single-cell RNA sequencing, deconstructed spermatogenesis occurring chimera testis. Collectively, this study details method exclusive xenogeneic germ production vivo, with implications may extend transgenesis, endangered species conservation efforts.
Язык: Английский
Процитировано
11
Protein & Cell, Год журнала: 2021, Номер 13(4), С. 234 - 238
Опубликована: Окт. 11, 2021
Язык: Английский
Процитировано
14
International Journal of Stem Cells, Год журнала: 2021, Номер 15(2), С. 113 - 121
Опубликована: Окт. 29, 2021
The ultimate goal of regenerative medicine is to replace damaged cells, tissues or whole organs, in order restore their proper function. Stem cell related technologies promise generate transplants from the patients' own cells. Novel approaches such as blastocyst complementation combined with genome editing techniques open up new perspectives for organ replacement therapies. This review summarizes recent advances field and highlights challenges that still remain be addressed.
Язык: Английский
Процитировано
13
Cold Spring Harbor Perspectives in Biology, Год журнала: 2021, Номер 14(10), С. a040808 - a040808
Опубликована: Дек. 6, 2021
Hannah Shelby, Tara Shelby and Marius Wernig Departments of Pathology Chemical Systems Biology, Institute for Stem Cell Biology Regenerative Medicine, Stanford University School Stanford, California 94305, USA Correspondence: wernig{at}stanford.edu
Язык: Английский
Процитировано
13
Frontiers in Immunology, Год журнала: 2022, Номер 13
Опубликована: Фев. 15, 2022
Background Animal fetal kidneys have the potential to be used as scaffolds for organ regeneration. We generated interspecies chimeric renal organoids by adding heterologous rat progenitor cells single from mouse and applying development mechanism of fetuses examine whether can differentiate into tissues three cell lineages between different species. Furthermore, we investigated with an increased proportion recipient reduce xenogeneic rejection. Methods C57BL/6JJmsSlc mice (B6 mice) Sprague-Dawley-Tg (CAG-EGFP) (GFP rats) were donors, mature male NOD/Shi-scid, IL-2RγKO Jic (NOG Sprague-Dawley rats (SD recipients. First, removed E13.5 B6 or E15.5 GFP enzymatically dissociated cells. These then mixed in equal proportions produce vitro . The transplanted under capsule NOG mice, maturation was observed histologically. prepared changing ratio derived SD subjected mild immunosuppression pathologically analyze strength immune response. Results cap mesenchyme reconstructed , nephron ureteric buds mosaically comprised GFP-negative GFP-positive In vivo environment immunodeficient differentiated matured lineages. Chimeric high rates showed milder rejection than complete xenograft organoids. vessels entered periphery organoids, which might their immunogenicity. Conclusion Interspecies may each lineage. they transplant compared
Язык: Английский
Процитировано
9