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ACS Biomaterials Science & Engineering Feb 2020Stem cell technology can be used in tissue engineering and regenerative medicine to transplant stem cells of somatic, embryonic, or induced pluripotent origin, which...
Stem cell technology can be used in tissue engineering and regenerative medicine to transplant stem cells of somatic, embryonic, or induced pluripotent origin, which have tremendous potential for the treatment of currently incurable diseases. Stem cells can maintain their stemness through their self-renewal capability while promoting tissue repair and regeneration through differentiation into various target tissue cells. These two major processes of stem cell biology are precisely regulated via extracellular and intracellular signals. Gaseous signaling molecules have recently been identified to play important roles in both physiology and pathophysiology, and inhalable nitric oxide (iNO) has even been applied as a therapeutic agent. Compared with chemical formulations, these molecules have lower molecular weights and are more likely to pass through the blood-brain barrier and between cells. Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (HS), three major gaseous signaling molecules involved in biological functions, are emerging as regulators of stem cell processes such as self-renewal, differentiation, survival, anti-apoptotic effects, proliferation, and immune rejection. Although many reviews concerning the roles of gaseous signaling molecules in different diseases or systems are available, few have focused on the roles of these molecules in the regulation of stem cells. Therefore, the aim of this paper is to systematically review the current literature on the functions and mechanisms of the gaseous signaling molecules NO, HS, and CO in different types of stem cells and to summarize the effects of these molecules on stem cell biology and in therapy.
Topics: Carbon Monoxide; Gases; Hydrogen Sulfide; Nitric Oxide; Stem Cells
PubMed: 33464852
DOI: 10.1021/acsbiomaterials.9b01681 -
Annals of Hematology May 2020Fanconi anemia (FA) is a DNA repair disorder resulting from mutations in genes encoding for FA DNA repair complex components and is characterized by variable congenital...
Fanconi anemia (FA) is a DNA repair disorder resulting from mutations in genes encoding for FA DNA repair complex components and is characterized by variable congenital abnormalities, bone marrow failure (BMF), and high incidences of malignancies. FA mosaicism arises from reversion or other compensatory mutations in hematopoietic cells and may be associated with BMF reversal and decreased blood cell sensitivity to DNA-damaging agents (clastogens); this sensitivity is a phenotypic and diagnostic hallmark of FA. Uncertainty regarding the clinical significance of FA mosaicism persists; in some cases, patients have survived multiple decades without BMF or hematologic malignancy, and in others hematologic failure occurred despite the presence of clastogen-resistant cell populations. Assessment of mosaicism is further complicated because clinical evaluation is frequently based on clastogen resistance in lymphocytes, which may arise from reversion events both in lymphoid-specific lineages and in more pluripotent hematopoietic stem/progenitor cells (HSPCs). In this review, we describe diagnostic methods and outcomes in published mosaicism series, including the substantial intervals (1-6 years) over which blood counts normalized, and the relatively favorable clinical course in cases where clastogen resistance was demonstrated in bone marrow progenitors. We also analyzed published FA mosaic cases with emphasis on long-term clinical outcomes when blood count normalization was identified. Blood count normalization in FA mosaicism likely arises from reversion events in long-term primitive HSPCs and is associated with low incidences of BMF or hematologic malignancy. These observations have ramifications for current investigational therapeutic programs in FA intended to enable gene correction in long-term repopulating HSPCs.
Topics: Bone Marrow Cells; Fanconi Anemia; Hematologic Neoplasms; Hematopoietic Stem Cells; Humans; Mosaicism
PubMed: 32065290
DOI: 10.1007/s00277-020-03954-2 -
Frontiers in Endocrinology 2022Hypothyroidism is a common hormone deficiency disorder. Although hormone supplemental therapy can be easily performed by daily levothyroxine administration, a proportion...
BACKGROUND
Hypothyroidism is a common hormone deficiency disorder. Although hormone supplemental therapy can be easily performed by daily levothyroxine administration, a proportion of patients suffer from persisting complaints due to unbalanced hormone levels, leaving room for new therapeutic strategies, such as tissue engineering and regenerative medicine.
METHODS
Electronic searches of databases for studies of thyroid regeneration or thyroid organoids were performed. A systematic review including both and models of thyroid regenerative medicine was conducted.
RESULTS
Sixty-six independent studies published between 1959 and May 1st, 2022 were included in the current systematic review. Among these 66 studies, the most commonly involved species was human (19 studies), followed by mouse (18 studies), swine (14 studies), rat (13 studies), calf/bovine (4 studies), sheep/lamb (4 studies) and chick (1 study). In addition, in these experiments, the most frequently utilized tissue source was adult thyroid tissue (46 studies), followed by embryonic stem cells (ESCs)/pluripotent stem cells (iPSCs) (10 studies), rat thyroid cell lines (7 studies), embryonic thyroid tissue (2 studies) and newborn or fetal thyroid tissue (2 studies). Sixty-three studies reported relevant thyroid follicular regeneration experiments , while 21 studies showed an experiment section that included transplanting engineered thyroid tissue into recipients. Together, 12 studies were carried out using 2D structures, while 50 studies constructed 3D structures.
CONCLUSIONS
Each aspect of thyroid regenerative medicine was comprehensively described in this review. The recovery of optimal hormonal equilibrium by the transplantation of an engineered functional thyroid holds great therapeutic promise.
Topics: Animals; Humans; Sheep; Cattle; Mice; Rats; Swine; Hypothyroidism; Pluripotent Stem Cells; Induced Pluripotent Stem Cells; Hormones
PubMed: 36531472
DOI: 10.3389/fendo.2022.1065410 -
Expert Review of Gastroenterology &... Mar 2020: Hepatocyte transplantation (HT) is a promising alternative to liver transplantation for the treatment of liver-based metabolic diseases and acute liver failure (ALF)....
: Hepatocyte transplantation (HT) is a promising alternative to liver transplantation for the treatment of liver-based metabolic diseases and acute liver failure (ALF). However, shortage of good-quality liver tissues, early cell loss post-infusion, reduced cell engraftment and function restricts clinical application.: A comprehensive literature search was performed to cover pre-clinical and clinical HT studies. The review discusses the latest developments to address HT limitations: cell sources from marginal/suboptimal donors to neonatal livers, differentiating pluripotent stem cells into hepatocyte-like cells, expansion, prevention of immune response to transplanted cells by encapsulation or using innate immunity-inhibiting agents, and enhancing engraftment through partial hepatectomy or irradiation.: To date, published data are highly encouraging specially the alginate-encapsulated hepatocyte treatment of children with ALF. Hepatocyte functions can be further improved through co-culturing with mesenchymal stromal cells. Moreover, genetic correction will enable the use of autologous cells in future personalized medicine.
Topics: Cell Transplantation; Cells, Cultured; Hepatocytes; Humans; Liver Diseases; Liver Transplantation
PubMed: 32098516
DOI: 10.1080/17474124.2020.1733975