Background Organ transplantation is predicted to increase as life expectancy and the incidence of chronic diseases rises. Regenerative medicine‐inspired technologies challenge the efficacy of the current allograft transplantation model. Methods A literature review was conducted using the PubMed interface of MEDLINE from the National Library of Medicine. Results were examined for relevance to innovations of organ bioengineering to inform analysis of advances in regenerative medicine affecting organ transplantation. Data reports from the Scientific Registry of Transplant Recipient and Organ Procurement Transplantation Network from 2008 to 2019 of kidney, pancreas, liver, heart, lung and intestine transplants performed, and patients currently on waiting lists for respective organs, were reviewed to demonstrate the shortage and need for transplantable organs. Results Regenerative medicine technologies aim to repair and regenerate poorly functioning organs. One goal is to achieve an immunosuppression‐free state to improve quality of life, reduce complications and toxicities, and eliminate the cost of lifelong antirejection therapy. Innovative strategies include decellularization to fabricate acellular scaffolds that will be used as a template for organ manufacturing, three‐dimensional printing and interspecies blastocyst complementation. Induced pluripotent stem cells are an innovation in stem cell technology which mitigate both the ethical concerns associated with embryonic stem cells and the limitation of other progenitor cells, which lack pluripotency. Regenerative medicine technologies hold promise in a wide array of fields and applications, such as promoting regeneration of native cell lines, growth of new tissue or organs, modelling of disease states, and augmenting the viability of existing ex vivo transplanted organs. Conclusion The future of organ bioengineering relies on furthering understanding of organogenesis, in vivo regeneration, regenerative immunology and long‐term monitoring of implanted bioengineered organs.
Purpose of Review In the current work, we will present the characterization of the main different stem cell-derived vesicular bioproducts with potential application in organ regeneration. Recent Findings The therapeutic effects of stem cell therapy in organ repair, specifically those utilizing mesenchymal stromal cells, are largely dependent on the cells' release of different bio-products. Among these bio-products, extracellular vesicles (EVs) appear to play a major role due to their ability to carry and deliver bioactive material for modulation of cellular pathways in recipient cells. Concurrently, mitochondria transfer emerged as a new mechanism of cell communication, in which the bioenergetics of a damaged cell are restored. Finally, apoptotic bodies released by dying apoptotic stem cells contribute to stimulation of the tissue's stem cells and modulation of the immune response. Summary Exploitation of isolated extracellular vesicles, mitochondria and apoptotic bodies in preclinical models of organ damage shows promising results. Here, we describe the results of the pre-clinical applications of stem cell vesicular products, as well as the first clinical trials approaching artificial administration of extracellular vesicles and mitochondria in human subjects and their possible benefits and limitations.
Intestinal microbiota is thought to play an important role in hepatic ischemia/reperfusion injury (IRI) after liver transplantation (LT). Rifaximin, a nonabsorbable antibiotic used to treat encephalopathy, exhibits antibacterial activity within the gut. We report the first study examining the impact of pre‐LT rifaximin use on reducing hepatic IRI and inflammatory cell infiltration after LT. This retrospective single‐center study included adult LT recipients from January 2013 through June 2016. Patients were divided into 2 groups based on duration of rifaximin use before LT: rifaximin group (≥28 days) and control group (none or <28 days). Patients receiving other antibiotics within 28 days of LT and re‐LTs were excluded. Outcomes and messenger RNA (mRNA) expression in the graft were compared by 1:1 propensity score–matching and multivariate analyses. On 1:1 matching (n = 39/group), rifaximin patients had lower postoperative serum transaminase levels and lower early allograft dysfunction (EAD; 10.3% versus 33.3%; P = 0.014). Of the matched patients, 8 patients (n = 4/group) had postreperfusion liver biopsies (approximately 2 hours after reperfusion) available for mRNA analysis. Hepatic expression of CD86 (macrophage marker) and cathepsin G (neutrophil marker) was significantly lower in rifaximin patients than controls (P < 0.05). The multivariate analysis included 458 patients. Rifaximin treatment <28 days was identified as an independent risk factor EAD in all patients and those with high Model for End‐Stage Liver Disease (MELD) score (MELD ≥35; n = 230). In conclusion, the propensity score–matched and multivariate analyses suggest a therapeutic role of rifaximin in reducing EAD. Pre‐LT rifaximin administration exerted a protective function against early liver injury, potentially by suppressing inflammatory cell activation in the graft.
The field of regenerative medicine is developing technologies that, in the near future, will offer alternative approaches to either cure diseases affecting the gastrointestinal tract or slow their progression by leveraging the intrinsic ability of our tissues and organs to repair after damage. This article will succinctly illustrate the three technologies that are closer to clinical translation-namely, human intestinal organoids, sphincter bioengineering and decellularization, whereby the cellular compartment of a given segment of the digestive tract is removed to obtain a scaffold consisting of the extracellular matrix. The latter will be used as a template for the regeneration of a functional organ, whereby the newly generated cellular compartment will be obtained from the patient's own cells. Although clinical application of this technology is approaching, product development challenges are being tackled to warrant safety and efficacy.
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