Over the past 20 years, and particularly in the last decade, significant developmental milestones have driven basic, translational, and clinical advances in the field of stem cell and regenerative medicine. In this article, we provide a systemic overview of the major recent discoveries in this exciting and rapidly developing field. We begin by discussing experimental advances in the generation and differentiation of pluripotent stem cells (PSCs), next moving to the maintenance of stem cells in different culture types, and finishing with a discussion of three-dimensional (3D) cell technology and future stem cell applications. Specifically, we highlight the following crucial domains: 1) sources of pluripotent cells; 2) next-generation in vivo direct reprogramming technology; 3) cell types derived from PSCs and the influence of genetic memory; 4) induction of pluripotency with genomic modifications; 5) construction of vectors with reprogramming factor combinations; 6) enhancing pluripotency with small molecules and genetic signaling pathways; 7) induction of cell reprogramming by RNA signaling; 8) induction and enhancement of pluripotency with chemicals; 9) maintenance of pluripotency and genomic stability in induced pluripotent stem cells (iPSCs); 10) feeder-free and xenon-free culture environments; 11) biomaterial applications in stem cell biology; 12) three-dimensional (3D) cell technology; 13) 3D bioprinting; 14) downstream stem cell applications; and 15) current ethical issues in stem cell and regenerative medicine. This review, encompassing the fundamental concepts of regenerative medicine, is intended to provide a comprehensive portrait of important progress in stem cell research and development. Innovative technologies and real-world applications are emphasized for readers interested in the exciting, promising, and challenging field of stem cells and those seeking guidance in planning future research direction.

Spinal cord injury (SCI) is a devastating neurological disorder that damages motor, sensory, and autonomic pathways. Recent advances in stem cell therapy have allowed for the in vitro generation of motor neurons (MNs) showing electrophysiological and synaptic activity, expression of canonical MN biomarkers, and the ability to graft into spinal lesions. Clinical translation, especially the transplantation of MN precursors in spinal lesions, has thus far been elusive because of stem cell heterogeneity and protocol variability, as well as a hostile microenvironment such as inflammation and scarring, which yield inconsistent pre-clinical results without a consensus best-practice therapeutic strategy. Induced pluripotent stem cells (iPSCs) in particular have lower ethical and immunogenic concerns than other stem cells, which could make them more clinically applicable. In this review, we focus on the differentiation of iPSCs into neural precursors, MN progenitors, mature MNs, and MN subtype fates. Previous reviews have summarized MN development and differentiation, but an up-to-date summary of technological and experimental advances holding promise for bench-to-bedside translation, especially those targeting individual MN subtypes in SCI, is currently lacking. We discuss biological mechanisms of MN lineage, recent experimental protocols and techniques for MN differentiation from iPSCs, and transplantation of neural precursors and MN lineage cells in spinal cord lesions to restore motor function. We emphasize efficient, clinically safe, and personalized strategies for the application of MN and their subtypes as therapy in spinal lesions.

Dysregulation of gene expression is a hallmark of aging. We examined epigenetic mechanisms that mediate aberrant expression of laminin genes in aging rat kidneys. In old animals, no alterations were found in the levels of abundant laminin mRNAs, whereas Lama3, b3, and c2 transcripts were increased compared to young animals. Lamc2 showed the strongest changes at the mRNA and protein levels. Lamc2 upregulation was transcriptional, as indicated by the elevated RNA polymerase II density at the gene. Furthermore, aging is associated with the loss of H3K27m3 and 5mC silencing modifications at the Lamc2 gene. Western blot analysis revealed no changes in cellular levels of H3K27m3 and cognate enzyme Ezh2 in old kidneys. Thus, the decrease in H3K27m3 at Lamc2 resulted from the re-distribution of this mark among genomic sites. Studies in kidney cells in vitro showed that reducing H3K27m3 density with Ezh2 inhibitor had no effect on Lamc2 expression, suggesting that this modification plays little role in gene upregulation in aging kidney. In contrast, treatment with DNA methylation inhibitor 2'-deoxy-5-azacytidine was sufficient to upregulate Lamc2 gene. We suggest that the loss of 5mC at silenced laminin genes drives their de-repression during aging, contributing to the age-related decline in renal function.

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Background: Arteriovenous fistulae (AVF) complicated by aneurysms are repaired through several mechanisms. Little is known about risk factors for aneurysm recurrence or the efficacy of subsequent repair of recurring aneurysms. Methods: About 291 patients underwent AVF aneurysm repair between 2009 and 2019 at a large urban medical center. Patients who underwent staged repair, had a primary graft with pseudoaneurysm, were status-post kidney transplant, or using other dialysis access at the time of repair were excluded. One hundred sixty-two patients were included in the study, of which 52 developed a secondary aneurysm. Chi-square and t-test analyses were used to compare demographics. Multivariate logistic regression was used to examine independent risk factors for aneurysm recurrence. Of the 52 patients with recurrent aneurysms, 41 were repaired again. Patency was examined for each group 1 year postoperatively. Results: Patients without secondary aneurysms were more likely to have a Charlson Comorbidity Index score ⩾5 ( p = 0.045). Males were 2.8 times more likely to develop a secondary aneurysm compared to females ( p = 0.023). Patients who underwent elective compared to emergent or urgent surgery for primary aneurysms were significantly less likely to recur (OR = 0.222; p = 0.016). Primary aneurysms repaired by end-to-end anastomosis, compared to aneurysmorrhaphy or graft, were significantly less likely to recur (OR = 0.239; p = 0.041). Among patients with secondary aneurysms, those repaired via end-to-end anastomosis had a significantly higher primary patency rate 1 year postoperatively ( p = 0.024). Secondary aneurysm repairs exhibited 1-year primary and secondary patency rates of 51.2% and 82.9%, respectively. Conclusions: End-to-end anastomosis reduces risk of recurrence and demonstrates superior patency rates when repairing recurrent aneurysms. It remains unclear why some patients are prone to aneurysm recurrence, however continued attempts to repair existing vascular access are proven to be successful.