A major unanswered question in autologous cell therapy is the appropriate timing for cell isolation. Many of the putative target diseases arise with old age and previous evidence, mainly from animal models, suggests that the stem/progenitor cell pool decreases steadily with age. Studies with human cells have been generally hampered to date by poor sample availability. In recent years, several laboratories have reported on the existence, both in rodents and humans, of skin-derived precursor (SKP) cells with the capacity to generate neural and mesodermal progenies. This easily obtainable multipotent cell population has raised expectations for their potential use in cell therapy of neurodegeneration. However, we still lack a clear understanding of the spatiotemporal abundance and phenotype of human SKPs. Here we show an analysis of human SKP abundance and in vitro differentiation potential, by using SKPs isolated from four distinct anatomic sites (abdomen, breast, foreskin, and scalp) from 102 healthy subjects aged 8 months to 85 years. Human SKP abundance and differentiation potential decrease sharply with age, being extremely difficult to isolate, expand, and differentiate when obtained from the elderly. Our data suggest preserving human SKP cell banks early in life would be desirable for use in clinical protocols in the aging population.
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http://dx.doi.org/10.1002/stem.27 | DOI Listing |
J Biol Chem
December 2024
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu, 226001, China. Electronic address:
Ischemia and hypoxia caused by vascular injury intensify nerve damage. Skin precursor-derived Schwann cells have demonstrated an accelerated in vivo pre-vascularization of tissue-engineered nerves. Furthermore, extracellular vesicles from skin precursor-derived Schwann cells (SKP-SC-EVs) show the potential in aiding peripheral nerve regeneration.
View Article and Find Full Text PDFCell
December 2024
Discovery Sciences, Novartis Biomedical Research, Basel, Switzerland. Electronic address:
Broad-complex, tramtrack, and bric-à-brac domain (BTB) and CNC homolog 1 (BACH1) is a key regulator of the cellular oxidative stress response and an oncogene that undergoes tight post-translational control by two distinct F-box ubiquitin ligases, SCF and SCF. However, how both ligases recognize BACH1 under oxidative stress is unclear. In our study, we elucidate the mechanism by which FBXO22 recognizes a quaternary degron in a domain-swapped β-sheet of the BACH1 BTB dimer.
View Article and Find Full Text PDFN Engl J Med
October 2024
From Baylor College of Medicine (S.P.L.) and the University of Texas M.D. Anderson Cancer Center (A.M.K.), Houston, the University of Texas Health San Antonio (R.S.S.) and CHRISTUS Santa Rosa Medical Center Hospital (I.M.T.), San Antonio, and the University of Texas Southwestern Medical Center, Dallas (A.I.S.) - all in Texas; Stanford University, Stanford (E.S.), Norris Comprehensive Cancer Center, University of Southern California, Los Angeles (S.D., A.S.), and City of Hope Medical Center, Duarte (S.K.P.) - all in California; SWOG Statistics and Data Management Center and Fred Hutchinson Cancer Center - both in Seattle (C.T., M.P.); the Ohio State University, Columbus (K.S.P.); the University of Chicago, Chicago (N.D.S.); McGill University Health Center, Montreal (W.K.); the Bladder Cancer Advocacy Network, SWOG Advocates, Pittsford, NY (R.B.); Oregon Health and Science University, Portland (T.M.K.); the University of Michigan, Ann Arbor (A.A.); the University of Colorado, Aurora (F.G.L.R.); Brigham and Women's Hospital, Boston (A.S.K.); Fox Chase Cancer Center, Philadelphia (D.J.C.); and Oschsner Medical Center, Jefferson, LA (D.J.C.).
Background: Whether extended lymphadenectomy is associated with improved disease-free and overall survival, as compared with standard lymphadenectomy, among patients with localized muscle-invasive bladder cancer undergoing radical cystectomy is unclear.
Methods: We randomly assigned, in a 1:1 ratio, patients with localized muscle-invasive bladder cancer of clinical stage T2 (confined to muscle) to T4a (invading adjacent organs) with two or fewer positive nodes (N0, N1, or N2) to undergo bilateral standard lymphadenectomy (dissection of lymph nodes on both sides of the pelvis) or extended lymphadenectomy involving removal of common iliac, presciatic, and presacral nodes. Randomization was performed during surgery and stratified according to the receipt and type of neoadjuvant chemotherapy, tumor stage (T2 vs.
Exp Dermatol
November 2024
Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Skin-derived precursor (SKPs) cells are multipotent stem cells found in the dermis that contribute to wound healing and induce hair follicle neogenesis when transplanted. The clinical application of adult human SKPs, however, is hindered by their loss of potency after in vitro expansion. To overcome this challenge, we aimed to isolate SKPs from human-induced pluripotent stem cell-derived skin organoids (SKOs), to enable mass production of these cells for therapeutics.
View Article and Find Full Text PDFCirc Heart Fail
December 2024
Departments of Medicine, Radiology, and Pathology, Brigham and Women's Hospital, Boston, MA (R.Y.K., M.J.-H., P.J., C.Y.H.).
Background: Hypertrophic cardiomyopathy (HCM) is a heterogeneous condition that can lead to atrial fibrillation, heart failure, and sudden cardiac death in many individuals but mild clinical impact in others. The mechanisms underlying this phenotypic heterogeneity are not well defined. The aim of this study was to use plasma proteomic profiling to help illuminate biomarkers that reflect or inform the heterogeneity observed in HCM.
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