A significant lack of donor organs restricts the opportunity to obtain tissue-specific scaffolds for tissue-engineering technologies. One of the acceptable solutions is the development of decellularization protocols for a human donor pancreas unsuitable for transplantation. A protocol of obtaining a biocompatible tissue-specific scaffold from decellularized fragments with pronounced human pancreas lipomatosis signs with preserved basic fibrillary proteins of a pancreatic tissue extracellular matrix was developed. The scaffold supports the adhesion and proliferation of human adipose derived stem cell (hADSCs) and prolongs the viability and insulin-producing function of pancreatic islets. Experiments conducted allow for the reliance on the prospects of using the donor pancreas unsuitable for transplantation in the technologies of tissue engineering and regenerative medicine, including the development of a tissue equivalent of a pancreas.
Organ transplantation continues to be the gold standard for saving the lives of patients with end-stage organ diseases. Its goal is to help recipients live longer and better lives. However, despite advancements, organ transplantation still faces serious challenges, such as organ shortage and the effects of chronic immunosuppression. In this regard, there is ongoing vigorous search for therapeutic strategies that can improve the efficacy of allogeneic organ transplantation. Mesenchymal stems cells (MSCs) can significantly enhance and accelerate regenerative processes in damaged organs, can angiogenesis angiogenesis and inhibit cell apoptosis, inflammation and fibrosis formation, and have immunomodulatory properties. Researchers and physicians are interested in MSCs because of a set of unique properties that could be useful in solid organ transplantation. This review critically analyzes and summarizes the actual clinical data related to the study of the therapeutic effects of MSCs in organ transplantation. Electronic databases Medline/PubMed (www/ncbi.nlm.nih.gov/pubmed) and eLIBRARY/Russian Science Citation Index (https://www.elibrary.ru) were searched for relevant literature. Inclusion criteria were clinical use of MSCs to improve the condition of kidney, liver, lung, heart and pancreas recipients, and to enhance graft quality. Exclusion criteria for articles included the use of MSCs for the treatment of non-transplant patients, as well as articles detailing the effects of MSCs products (exosomes, vesicles and conditioned media) and research studies conducted in vitro and in vivo (without patient participation), conference proceedings, reviews and preprints of articles. Thirty-one original articles in English and Russian languages were selected for literature review. The prospects of MSCs in transplantology are also covered in the paper.
23 April 2020 in Russian Journal of Transplantology and Artificial Organs
Producing a tissue-engineered pancreas based on a tissue-specific scaffold from a decellularized pancreas, imitating the natural pancreatic tissue microenvironment and the islets of Langerhans, is one of the approaches to treating patients with type 1 diabetes mellitus (T1DM). The aim of this work was to investigate the ability of a fine-dispersed tissue-specific scaffold (DP scaffold) from decellularized human pancreas fragments to support the islets’ survival and insulin-producing function when injected in a streptozotocin-induced diabetic rat model. The developed decellularization protocol allows us to obtain a scaffold with a low DNA content (33 [26; 38] ng/mg of tissue, p < 0.05) and with the preservation of GAGs (0.92 [0.84; 1.16] µg/mg, p < 0.05) and fibrillar collagen (273.7 [241.2; 303.0] µg/mg, p < 0.05). Rat islets of Langerhans were seeded in the obtained scaffolds. The rats with stable T1DM were treated by intraperitoneal injections of rat islets alone and islets seeded on the DP scaffold. The blood glucose level was determined for 10 weeks with a histological examination of experimental animals’ pancreas. A more pronounced decrease in the recipient rats’ glycemia was detected after comparing the islets seeded on the DP scaffold with the control injection (by 71.4% and 51.2%, respectively). It has been shown that the DP scaffold facilitates a longer survival and the efficient function of pancreatic islets in vivo and can be used to engineer a pancreas.