Repository Of Stem Cells Research Articles

Dental Stem Cell-Based Therapy for Glycemic Control and the Scope of Clinical Translation: A Systematic Review and Meta-Analysis

Background: The tooth is a repository of stem cells, garnering interest in recent years for its therapeutic potential. The aim of this systematic review and meta-analysis was to test the hypothesis that dental stem cell administration can reduce blood glucose and ameliorate polyneuropathy in diabetes mellitus. The scope of clinical translation was also assessed. Methods: PubMed, Cochrane, Ovid, Web of Science, and Scopus databases were searched for animal studies that were published in or before July 2023. A search was conducted in OpenGrey for unpublished manuscripts. Subgroup analyses were performed to identify potential sources of heterogeneity among studies. The risk for publication bias was assessed by funnel plot, regression, and rank correlation tests. Internal validity, external validity, and translation potential were determined using the SYRCLE (Systematic Review Center for Laboratory Animal Experimentation) risk of bias tool and comparative analysis. Results: Out of 5031 initial records identified, 17 animal studies were included in the review. There was a significant decrease in blood glucose in diabetes-induced animals following DSC administration compared to that observed with saline or vehicle (SMD: −3.905; 95% CI: −5.633 to −2.177; p = 0.0004). The improvement in sensory nerve conduction velocity (SMD: 4.4952; 95% CI: 0.5959 to 8.3945; p = 0.035) and capillary-muscle ratio (SMD: 2.4027; 95% CI: 0.8923 to 3.9132; p = 0.0095) was significant. However, motor nerve conduction velocity (SMD: 3.1001; 95% CI: −1.4558 to 7.6559; p = 0.119) and intra-epidermal nerve fiber ratio (SMD: 1.8802; 95% CI: −0.4809 to 4.2413; p = 0.0915) did not increase significantly. Regression (p < 0.0001) and rank correlation (p = 0.0018) tests indicated the presence of funnel plot asymmetry. Due to disparate number of studies in subgroups, the analyses could not reliably explain the sources of heterogeneity. Interpretation: The direction of the data indicates that DSCs can provide good glycemic control in diabetic animals. However, methodological and reporting quality of preclinical studies, heterogeneity, risk of publication bias, and species differences may hamper translation to humans. Appropriate dose, mode of administration, and preparation must be ascertained for safe and effective use in humans. Longer-duration studies that reflect disease complexity and help predict treatment outcomes in clinical settings are warranted. This review is registered in PROSPERO (number CRD42023423423).

Harshening stem cell research and precision medicine: The states of human pluripotent cells stem cell repository diversity, and racial and sex differences in transcriptomes.

In vitro investigation on human development, disease modeling, and drug discovery has been empowered by human induced pluripotent stem cell (hiPSC) technologies that form the foundation of precision medicine. Race and sex genetic backgrounds have become a major focus of many diseases modeling and drug response evaluation in the pharmaceutical industry. Here, we gathered data from major stem cell repositories to analyze the diversity with respect to ethnicity, sex, and disease types; and we also analyzed public datasets to unravel transcriptomics differences between samples of different ethnicities and sexes. We found a lack of diversity despite the large sample size of human induced pluripotent stem cells. In the ethnic comparison, the White group made up the majority of the banked hiPSCs. Similarly, for the organ/disease type and sex comparisons, the neural and male hiPSCs accounted for the majority of currently available hiPSCs. Bulk RNA-seq and single-cell transcriptomic analysis coupled with Machine Learning and Network Analysis revealed panels of gene features differently expressed in healthy hiPSCs and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) of different races and sexes. The data highlights the current ethnic and sex inequality in stem cell research and demonstrates the molecular biological diversity of hiPSCs and cardiomyocytes from different races and genders. We postulate that future efforts in stem cell biology, regenerative and precision medicine should be guided towards an inclusive, diverse repository reflecting the prevalence of diseases across racial and ethnic groups and the sexes, important for both common and rare disease modeling, drug screening, and cell therapeutics.

"Basal Cell Migration" in Regeneration of the Corneal Wound-Bed.

In this issue of Stem Cell Reports, Park et al. (2019) describe real-time in vivo visual monitoring of keratin-14+, Confetti-labeled limbal epithelial stem cells and their progeny as they contribute to central corneal wound-healing. The authors show that corneal wounds initially heal by “basal epithelial cell migration” into the wound-bed.

Dynamic expression of SMAD3 is critical inosteoblast differentiation of PDMCs.

Human pluripotent stem cells have the potential assist in the identification of genes involved in mammalian development. The human placenta is considered a repository of stem cells, termed placenta‑derived multipotent cells (PDMCs), which are able to differentiate into cells with an osteoblastic phenotype. This plasticity of PDMCs maybe applied clinically to the understanding of osteogenesis and osteoporosis. In the presentstudy, osteoblasts were generated by culturing PDMCs in osteogenic medium. Reverse transcription quantitative polymerase chain reactionand the degree of osteoblast calcification were used to evaluate the efficacy of osteogenesis. The results suggestedthat the expression of mothers against decapentaplegic homolog 3 (SMAD3) increased in the initial stages of osteogenic differentiation but decreased in the later stages. However, osteogenesis was inhibitedwhen the PDMCs overexpressed SMAD3 throughout the differentiation period. In addition, the rate of osteogenic differentiation was decreased when SMAD3 signaling was impaired. In conclusion, SMAD3 serves an important role in osteoblast differentiation and bone formation in a time‑dependent manner. The data from the present study indicate that arapid increase in SMAD3 expression is crucial for osteogenesis and suggest a role for PDMCs in the treatment of patients with osteoporosis.

Characterization of corneal stromal stem cells with the potential for epithelial transdifferentiation

IntroductionThe corneal stroma is being increasingly recognized as a repository for stem cells. Like the limbal and endothelial niches, stromal stem cells often reside in the peripheral cornea and limbus. These peripheral and limbal corneal stromal cells (PLCSCs) are known to produce mesenchymal stem cells in vitro. Recently, a common corneal stromal and epithelial progenitor was hinted at. This study aims to examine the stem cell potential of corneal stromal cells and to investigate their epithelial transdifferentiation ability.MethodsPLCSCs were grown in traditional Dulbecco modified Eagle medium (DMEM)-based keratocyte culture medium and an M199-based medium and analyzed for a profile of cell-surface markers by using flow cytometry and differentiated into mesenchymal phenotypes analyzed with quantitative polymerase chain reaction (qPCR) and histologic staining. PLCSCs in M199 were subsequently divided into subpopulations based on CD34 and CD105 expression by using fluorescence- activated cell sorting (FACS). Subpopulations were characterized by marker profile and mesenchymal differentiation ability. Both whole PLCSCs and subpopulations were also cultured for epithelial transdifferentiation.ResultsCells cultured in M199 demonstrated a more stem-like cell-surface marker profile, and the keratocyte marker CD34 was retained for several passages but absent in cells cultured in DMEM. Cells cultured in M199 also exhibited a greater mesenchymal differentiation potential, compared with DMEM. PLCSCs could be divided into CD34+CD105+, CD34-CD105+, and CD34-CD105- subpopulations, of which CD34+CD105+ cells were the most stemlike with regard to marker expression and mesenchymal differentiation potential. Subpopulations of PLCSCs exhibited differing abilities to transdifferentiate into epithelial phenotypes. Cells that were initially CD34+CD105+ showed the greatest differentiation potential, producing CK3+ and CK19+ cells, and expressed a range of both epithelial progenitor (HES1, FRZB1, DCT, SOD2, ABCG2, CDH1, KRT19) and terminally differentiated (DSG3, KRT3, KRT12, KRT24) genes.ConclusionsCulture medium has a significant effect on the phenotype and differentiation capacity of PLCSCs. The stroma contains a heterogeneous cell population in which we have identified CD34+ cells as a stem cell population with a capacity for mesenchymal and epithelial differentiation.

Coxsackievirus B3 Infects the Bone Marrow and Diminishes the Restorative Capacity of Erythroid and Lymphoid Progenitors

Coxsackievirus B3 (CVB3) is known to infect stem cells in the neonatal central nervous system. Here, we evaluated the effects of CVB3 infection on the major source and repository of stem cells, the bone marrow (BM). Viral genome was detectable in BM within 24 h of infection, and productive infection of BM cells was evident, peaking at 48 h postinfection (p.i.), when ∼1 to 2% of BM cells produced infectious virus particles. Beginning at 2 to 3 days p.i., a dramatic and persistent loss of immature erythroid cells, B and T lymphocytes, and neutrophils was observed in BM and, by day 3 to 4 p.i., the femoral BM stroma was largely destroyed. Analysis of peripheral blood revealed a modest neutrophilia, a loss of reticulocytes, and a massive lymphopenia. The abundance of multipotent progenitor cells (Lin(-)/c-kit(+)/Flt3(+)) in BM declined ∼10-fold during CVB3 infection and, consistent with a deficiency of primitive hematopoietic progenitors, serum levels of the hematopoietic growth factor Flt3 ligand were dramatically elevated. Therefore, we analyzed the regenerative capacity of BM from CVB3-infected mice. Granulocyte/macrophage progenitors displayed a relatively normal proliferative ability, consistent with the fact that the peripheral blood level of neutrophils-which are very short-lived cells-remained high throughout infection. However, erythroid and lymphoid hematopoietic progenitors in BM from CVB3-infected mice showed a markedly reduced colony-forming capacity, consonant with the observed loss of both lymphocytes and immature erythroid cells/reticulocytes from the BM and peripheral blood. In summary, CVB3 infects the BM and exerts differential effects on the various hematopoietic progenitor populations.

Laser synthesis and comparative testing of a three-dimensional porous matrix of titanium and titanium nickelide as a repository for stem cells

The paper discusses the prospects of layer-by-layer synthesis of porous tissue scaffolds (matrices) of titanium and NiTi (nitinol) as a repository for stem cells. The experiments are performed on primary cultures of human dermal fibroblasts of 4–18 passages. The culture of dermal fibroblasts is obtained from the skin and muscle tissue of 6 to 10-week abortuses with the method of primary explants. The role of surface morphology of porous matrices of these materials in cell adhesion and proliferation is examined in comparison with cast dental titanium. The surface microstructure and roughness are analyzed with optical and scanning electron microscopy before and after experiments in vitro. The elemental analysis is used to determine the biochemical composition of post-experimental porous matrix structures. The results show high chemotaxis of cells to the samples and effect of the matrix composition on the development of cell culture.

Miniaturized hairs maintain contact with the arrector pili muscle in alopecia areata but not in androgenetic alopecia: A model for reversible miniaturization and potential for hair regrowth

Background:Hair follicle miniaturization is the hallmark of male pattern hair loss (MPHL), female pattern hair loss (FPHL), and alopecia areata (AA). AA has the potential for complete hair regrowth and reversal of miniaturization. MPHL and FPHL are either irreversible or show only partial regrowth and minimal reversal of miniaturization. Hypothesis: The arrector pili muscle (APM) attachment to the hair follicle bulge, a recognized repository of stem cells may be necessary for reversal of hair follicle miniaturization.Materials and Methods:Sequential histological sections from MPHL, FPHL, AA, and telogen effluvium were used to create three-dimensional images to compare the relationship between the APM and bulge.Results:In AA, contact was maintained between the APM and the bulge of miniaturized follicles while in MPHL and FPHL contact was lost.Discussion:Contact between the APM and the bulge in AA may be required for reversal of hair follicle miniaturization. Maintenance of contact between miniaturized follicles in AA could explain the complete hair regrowth while loss of contact between the APM and the bulge in MPHL and FPHL may explain why the hair loss is largely irreversible. This loss of contact may reflect changes in stem cell biology that also underlie irreversible miniaturization.

Canine Follicle Stem Cell Candidates Reside in the Bulge and Share Characteristic Features with Human Bulge Cells

The hair follicle bulge has attracted great interest as a stem cell repository. Previous studies have focused on rodent or human bulge stem cells, and our understanding of those in other species is limited. In this study, we attempted to localize and characterize stem cell candidates in canine hair follicles. The canine skin xenografting study located label-retaining cells in the outer root sheath around the insertion point of the arrector pili muscle, where the immunoreactivity of human bulge markers, keratin 15 and follistatin, were detected. Canine bulge cell-enriched keratinocytes up-regulated human bulge biomarkers CD200 and DIO2, and conserved key cell regulators of bulge stem cells, such as SOX9 and LHX2. Importantly, canine bulge-derived keratinocytes were highly proliferative in vitro and, when combined with trichogenic dermal cells, reconstituted pilosebaceous structures as well as the epidermis in vivo. Successful detection of canine specific DNA sequences suggested that the regenerated tissue was of canine origin. In addition, canine specific bulge cell and sebocyte lineage markers were expressed in reconstituted pilosebaceous units, implying the multipotency of canine bulge cells. Our findings demonstrate a unique strategy utilizing canine bulge cells to investigate human stem cell biology and intractable hair disorders that involve the bulge region.

Amniotic Stem Cell International

Cells derived from the amniotic fluid for genetic diagnosis share many biological characteristics of stem cells. Recent studies at the single cell (clonal) level identified cells of the three embryonic germ layers in the amniotic fluid. It was therefore decided to establish an international non-profit alliance to create a repository of stem cells from the surplus cells remaining after completion of the cytogenetic analysis.

Vibrissa hair bulge houses two populations of skin epithelial stem cells distinct by their keratin profile

Defining the properties of postnatal stem cells is of interest given their relevance for tissue homeostasis and therapeutic applications, such as skin tissue engineering for burn patients. In hair follicles, the bulge region of the outer root sheath houses stem cells. We show that explants from the prominent bulge area, but not the bulb, in rodent vibrissa follicles can produce epidermis in a skin model of tissue engineering. Using morphological criteria and keratin expression, we typified epithelial stem cells of vibrissa bulge. Two types of slow-cycling cells (Bb, Bs1) featuring a high colony-forming capacity occur in the bulge. Bb cells are located in the outermost basal layer, express K5, K15, K17, and K19, and feature a loosely organized keratin network. Bs1 cells localize to the suprabasal layers proximal to Bb cells and express K5/K17, correlating with a network of densely bundled filaments. These prominent bundles are missing in K17-null mice, which lack vibrissa. Atypically, both the Bb and Bs1 keratinocytes lack K14 expression. These findings show heterogeneity within the hair follicle stem cell repository, establish that a subset of slow-cycling cells are suprabasal in location, and point to a special role for K5/K17 filaments in a newly defined subset of stem cells. Our results are discussed in the context of long-term survival of engineered tissues after grafting that requires the presence of stem cells.

Viewpoint 7

Viewpoint 7

Desmosomal proteins, including desmoglein 3, serve as novel negative markers for epidermal stem cell-containing population of keratinocytes.

No single method has been universally adopted for identifying and isolating epidermal stem/progenitor cells, and the emergence of new markers of stem cell populations is worth exploring. Here we report, for the first time, that clusters of basal keratinocytes at the tips of the rete ridges in human palm, previously recognised as a major repository of stem cells, had very low levels of desmoplakin protein and mRNA expression, compared with cells at the sides of the ridges or above the dermal papillae. We found that in populations of palm keratinocytes, selected by their ability to adhere rapidly to type IV collagen, there were significantly reduced levels of desmoplakin and other major desmosome proteins. We then showed that a low desmoglein 3 (Dsg3) expression on the cell surface could be used to enrich for a cell population with high clonogenecity, colony forming efficiency and enhanced proliferative potential, but with a low ability to form the abortive clones, compared with populations with a higher Dsg3 expression. Moreover, stringent sorting of populations showing both beta1 integrin-bright and Dsg3-dull expression enabled even further enrichment of a population containing the putative epidermal stem cells. These findings provide the basis for a new strategy for epidermal stem/progenitor cell enrichment, and encourage further study of the role of desmosomes in stem cell biology.

Scientific, logistical, and ethical issues related to creation of a stem cell repository for use in experimental trials of gene therapy for AIDS.

Scientific, logistical, and ethical issues related to creation of a stem cell repository for use in experimental trials of gene therapy for AIDS.

An analysis of thymic function and the possible role of the thymus in stem cell production

The thymus is considered to be essentially an organ of the immune system, its purpose being to supply T cells. The role of the T cell is to regulate the immune reaction which it does by liberating lymphokines. The lymphokine function of the T cells was not deciphered in vivo, but in explanted T cells, and it is debatable if explanted cells behave in the same way as their counterparts in the intact animal, so the liberated lymphokines may not represent nature's intent. Adding to the disquiet are those biological properties of the thymus which are difficult to explain on an immunological basis, in particular why the thymus is essential in the child but not in the adult. Thus, there is room for a different approach to the role of the thymus. There is sound evidence that the thymus plays a part in somatic growth and differentiation, and one explanation is that the thymus provides the stem cells for somatic growth. A stem cell role is supported by studies on mastopoiesis and eosinophilopoiesis, and also supported by the way embryonic organs grow after their initial development. From the arguments put forward, the hypothesis is put that the role of the thymus is to store and propagate the stem cells required for the organ growth which takes place subsequent to their initial development. If the thymus is a repository for stem cells, the varied aspects of thymic behaviour, including its role in immunity, can be explained. In particular, the hypothesis explains that aspect which is most mysterious, and that is why the thymus is essential in the child but not in the adult.