Adult Stem Cells Research Articles

Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone.

In the adult mammalian brain, neurons are produced from neural stem cells (NSCs) residing in two niches-the subventricular zone (SVZ), which forms the lining of the lateral ventricles, and the subgranular zone in the hippocampus. Epigenetic mechanisms contribute to maintaining distinct cell fates by suppressing gene expression that is required for deciding alternate cell fates. Several histone deacetylase (HDAC) inhibitors can affect adult neurogenesis in vivo. However, data regarding the role of specific HDACs in cell fate decisions remain limited. Herein, we demonstrate that HDAC8 participates in the regulation of the proliferation and differentiation of NSCs/neural progenitor cells (NPCs) in the adult mouse SVZ. Specific knockout of Hdac8 in NSCs/NPCs inhibited proliferation and neural differentiation. Treatment with the selective HDAC8 inhibitor PCI-34051 reduced the neurosphere size in cultures from the SVZ of adult mice. Further transcriptional datasets revealed that HDAC8 inhibition in adult SVZ cells disturbs biological processes, transcription factor networks, and key regulatory pathways. HDAC8 inhibition in adult SVZ neurospheres upregulated the cytokine-mediated signaling and downregulated the cell cycle pathway. In conclusion, HDAC8 participates in the regulation of in vivo proliferation and differentiation of NSCs/NPCs in the adult SVZ, which provides insights into the underlying molecular mechanisms.

An iron rheostat controls hematopoietic stem cell fate

Mechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularly during mitosis. To study the functional and molecular consequences of iron restriction, we developed models allowing for transient iron bioavailability limitation and combined single-molecule RNA quantification, metabolomics, and single-cell transcriptomic analyses with functional studies. Our data reveal that the activation of the limited iron response triggers coordinated metabolic and epigenetic events, establishing stemness-conferring gene regulation. Notably, we find that aging-associated cytoplasmic iron loading reversibly attenuates iron-dependent cell fate control, explicating intervention strategies for dysfunctional aged stem cells.

Control of muscle satellite cell function by specific exercise-induced cytokines and their applications in muscle maintenance.

Exercise is recognized to play an observable role in improving human health, especially in promoting muscle hypertrophy and intervening in muscle mass loss-related diseases, including sarcopenia. Recent rapid advances have demonstrated that exercise induces the release of abundant cytokines from several tissues (e.g., liver, muscle, and adipose tissue), and multiple cytokines improve the functions or expand the numbers of adult stem cells, providing candidate cytokines for alleviating a wide range of diseases. Muscle satellite cells (SCs) are a population of muscle stem cells that are mitotically quiescent but exit from the dormancy state to become activated in response to physical stimuli, after which SCs undergo asymmetric divisions to generate new SCs (stem cell pool maintenance) and commit to later differentiation into myocytes (skeletal muscle replenishment). SCs are essential for the postnatal growth, maintenance, and regeneration of skeletal muscle. Emerging evidence reveals that exercise regulates muscle function largely via the exercise-induced cytokines that govern SC potential, but this phenomenon is complicated and confusing. This review provides a comprehensive integrative overview of the identified exercise-induced cytokines and the roles of these cytokines in SC function, providing a more complete picture regarding the mechanism of SC homeostasis and rejuvenation therapies for skeletal muscle.

Coral Tissue Regeneration and Growth Is Associated with the Presence of Stem-like Cells

Members of the Cnidaria phylum were studied for centuries to depict the source of their unprecedented regeneration capacity. Although adult stem cells (ASCs) have been recognized in tissue growth/regeneration in many hydrozoans, there has not been any evidence of them in the ancestral Anthozoa class. This study sheds light on the development of epidermal epithelium expansion, akin to blastema, during tissue regeneration after small circular incisions (each 2.77 mm2) and during the natural expansion of tissue across a flat surface in the scleractinian coral Stylophora pistillata. Regeneration was completed within 9 days in 84.5% (n = 64) of the assays. About 35% of the samples regrew a single polyp, 60% showed no polyp regrowth, and approximately 6% exhibited multiple new polyps. We further used histological staining, pH3, Piwi immuno-histochemistry, and qPCR for eight stemness markers: Piwi-1, Nanos-1, Nanos-1-like, Tudor-5, Tudor-7, Boule, Sox-2, and Myc-1. The results revealed the formation of an “addendum”, an epidermal epithelium in the growing edges (in regenerating and normal-growing fronts) inhabited by a cluster of small cells featuring dense nuclei, resembling ASCs, many expressing pH3 as well as Piwi proteins. Most of the stemness genes tested were upregulated. These results indicate the participation of ASCs-like cells in tissue regeneration and growth in scleractinian corals.

Dissecting the spatiotemporal diversity of adult neural stem cells.

Adult stem cells are important for tissue turnover and regeneration. However, in most adult systems it remains elusive how stem cells assume different functional states and support spatially patterned tissue architecture. Here, we dissected the diversity of neural stem cells in the adult zebrafish brain, an organ that is characterized by pronounced zonation and high regenerative capacity. We combined single-cell transcriptomics of dissected brain regions with massively parallel lineage tracing and in vivo RNA metabolic labeling to analyze the regulation of neural stem cells in space and time. We detected a large diversity of neural stem cells, with some subtypes being restricted to a single brain region, while others were found globally across the brain. Global stem cell states are linked to neurogenic differentiation, with different states being involved in proliferative and non-proliferative differentiation. Our work reveals principles of adult stem cell organization and establishes a resource for the functional manipulation of neural stem cell subtypes.

Therapeutic Potential in Wound Healing of Allogeneic Use of Equine Umbilical Cord Mesenchymal Stem Cells.

Wound healing after skin injury is a complex process, particularly in equines where leg wounds are prevalent and their repair is complicated due to the anatomical characteristics. Conventional treatments are not effective enough. The umbilical cord offers an unlimited source of adult mesenchymal stem cells (ucMSCs) from Wharton's jelly tissue. The present study aims to demonstrate the safety and therapeutic potential of the allogeneic use of equine ucMSCs (e-ucMSCs) in the healing of severe equine leg wounds. The methods employed were the isolation, culture and expansion of e-ucMSCs. Flow cytometry and a PCR assay were used for cell characterization. This study included an immunomodulation assay, a murine pre-clinical trial and the first phase of an equine clinical trial. Our results showed that e-ucMSCs express a functional HLA-G homolog, EQMHCB2. In the immunomodulation assay, the e-ucMSCs inhibited the proliferation of activated equine peripheral blood mononuclear cells (e-PBMCs). In the murine pre-clinical trial, e-ucMSCs reduced healing time by 50%. In the equine clinical trial, the injection of e-ucMSCs into severe leg lesions improved the closure time and quality of the tissues involved, regenerating them without fibrous tissue scar formation. In conclusion, the results of this study suggest that e-ucMSCs can be used allogeneically for wound healing by creating a tolerogenic environment.

The neuronal transcription factor MEIS2 is a calpain-2 protease target.

Tight control over transcription factor activity is necessary for a sensible balance between cellular proliferation and differentiation in the embryo and during tissue homeostasis by adult stem cells, but mechanistic details have remained incomplete. The homeodomain transcription factor MEIS2 is an important regulator of neurogenesis in the ventricular-subventricular zone (V-SVZ) adult stem cell niche in mice. We here identify MEIS2 as direct target of the intracellular protease calpain-2 (composed of the catalytic subunit CAPN2 and the regulatory subunit CAPNS1). Phosphorylation at conserved serine and/or threonine residues, or dimerization with PBX1, reduced the sensitivity of MEIS2 towards cleavage by calpain-2. In the adult V-SVZ, calpain-2 activity is high in stem and progenitor cells, but rapidly declines during neuronal differentiation, which is accompanied by increased stability of MEIS2 full-length protein. In accordance with this, blocking calpain-2 activity in stem and progenitor cells, or overexpression of a cleavage-insensitive form of MEIS2, increased the production of neurons, whereas overexpression of a catalytically active CAPN2 reduced it. Collectively, our results support a key role for calpain-2 in controlling the output of adult V-SVZ neural stem and progenitor cells through cleavage of the neuronal fate determinant MEIS2.

Engraftment of adult hematopoietic stem and progenitor cells in a novel model of humanized mice

Pre-clinical use of humanized mice transplanted with CD34+ hematopoietic stem and progenitor cells (HSPCs) is limited by insufficient engraftment with adult non-mobilized HSPCs. Here, we developed a novel immunodeficient mice based on NOD-SCID-Il2γc-/- (NSG) mice to support long-term engraftment with human adult HSPCs. As both Flt3L and IL-6 are critical for many aspects of hematopoiesis, we knock-out mouse Flt3 and knock-in human IL6 gene. The resulting mice showed an increase in the availability of mouse Flt3L to human cells and a dose-dependent production of human IL-6 upon activation. Upon transplantation with low number of human HSPCs from adult bone marrow, these humanized mice demonstrated a significantly higher engraftment with multilineage differentiation of human lymphoid and myeloid cells, and tissue colonization at one year after adult HSPC transplant. Thus, these mice enable studies of human hematopoiesis and tissue colonization over time and may facilitate building autologous models for immuno-oncology studies.

A162 DEFINING INNATE IMMUNE CELL MECHANISMS UPON HELICOBACTER PYLORI MEDIATED TUMORIGENESIS

Abstract Aims Hypothesis: H. pylori interacts with eosinophils to inhibit degranulation, alter eosinophil gene expression and promote gastric tumorigenesis Aim 1: Elucidate the mechanisms underlying the interactions between eosinophils and H. pylori. Aim 2: Determine the role of eosinophils during H. pylori mediated gastric tumorigenesis. Methods Histological and immunofluorescent staining. Hemotoxilin and eosin staining is important to analyze gastric gland structure and parietal cell loss. Immunofluorescent staining is used to detect and localize specific antigens present in cells and cell membranes. Gastric organoids: Gastric organoids are an important tool for modelling dissease. Gastric organoids generated from adult stem cells from gastric glands depend on growth factors that mimic tissue regeneration. Bone marrow derived eosinophils: Bone marrow progenitor cells isolated from murine femur and tibia are easily converted into maturer eosinophils with the addition of cytokine interleukin-5. Results Addition of mouse derived eosinophils to gastric organoids significantly increases number of organoids. To understand the relationship between eosinophils and gastric epithelial cell (GEC) growth, I designed a co-culture experiment that involved incubating mature eosinophils with gastric glands in an extracellular matrix. These findings revealed a significant increase in the number of gastric organoids per well when eosinophils were present compared to the gastric organoids without eosinophils. This observation supports the hypothesis that eosinophils may play a crucial role in promoting gastric tumorigenesis. Exposure of mouse derived eosinophils to H. pylori significantly increases gastric organoid proliferation. To explore the impact of stimulating eosinophils prior to incubation with GECs I incubated the eosinophils with H. pylori. As expected, there was a significant increase in the number of organoids per well with the addition of uninfected eosinophils. Interestingly, when H. pylori incubated eosinophils were added to the gastric glands, there was a significant increase in the number of gastric organoids per well compared to uninfected eosinophils. Conclusions My preliminary findings have indicated that eosinophils can promote gastric epithelial stem cell proliferation. These results led me to ask how treatment of eosinophils with H. pylori subsequently impacts gastric organoid growth and gastric stem cell proliferation. Interestingly, I found H. pylori treated eosinophils increase growth and gastric stem cell proliferation. These results support my hypothesis as increased proliferation is considered a hallmark of tumorigenesis. There little known about resident and inflammatory GI eosinophils and the role of eosinophils during tumorigenesis in unknown. A better understanding of the role eosinophils play can uncover novel mechanisms to be targeted for therapeutic intervention. Funding Agencies CIHR

Substrate-bound and soluble domains of tenascin-C regulate differentiation, proliferation and migration of neural stem and progenitor cells.

The lack of regenerative capacity of the central nervous system is one of the major challenges nowadays. The knowledge of guidance cues that trigger differentiation, proliferation, and migration of neural stem and progenitor cells is one key element in regenerative medicine. The extracellular matrix protein tenascin-C (Tnc) is a promising candidate to regulate cell fate due to its expression in the developing central nervous system and in the adult neural stem cell niches. Of special interest are the alternatively spliced fibronectin type III (FnIII) domains of Tnc whose combinatorial diversity could theoretically generate up to 64 isoforms in the mouse. A total of 27 isoforms have already been discovered in the developing brain, among others the domain combinations A1D, CD, and A124BCD. In the present study, these domains as well as the combination of the constitutively expressed FnIII domains 7 and 8 (78) were expressed in Chinese hamster ovary cells as pseudo-antibodies fused to the Fc-fragment of a human immunoglobulin G antibody. The fusion proteins were presented to primary mouse neural stem/progenitor cells (NSPCs) grown as neurospheres, either as coated culture substrates or as soluble additives in vitro. The influence of the domains on the differentiation, proliferation and migration of NSPCs was analyzed. We observed that the domain combination A124BCD promoted the differentiation of neurons and oligodendrocytes, whereas the domain A1D supported astrocyte differentiation. The constitutively expressed domain 78 had a proliferation and migration stimulating impact. Moreover, most effects were seen only in one of the presentation modes but not in both, suggesting different effects of the Tnc domains in two- and three-dimensional cultures. This knowledge about the different effect of the Tnc domains might be used to create artificial three-dimensional environments for cell transplantation. Hydrogels spiked with Tnc-domains might represent a promising tool in regenerative medicine.

Endometrial mesenchymal stromal/stem cells improve regeneration of injured endometrium in mice

BackgroundThe monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown.MethodsElectrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test.ResultsHuman eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining.ConclusionsOur findings suggest eMSC improves regeneration of injured endometrium in mice.

Coordination between circadian neural circuit and intracellular molecular clock ensures rhythmic activation of adult neural stem cells

The circadian clock throughout the day organizes the activity of neural stem cells (NSCs) in the dentate gyrus (DG) of adult hippocampus temporally. However, it is still unclear whether and how circadian signals from the niches contribute to daily rhythmic variation of NSC activation. Here, we show that norepinephrinergic (NEergic) projections from the locus coeruleus (LC), a brain arousal system, innervate into adult DG, where daily rhythmic release of norepinephrine (NE) from the LC NEergic neurons controlled circadian variation of NSC activation through β3-adrenoceptors. Disrupted circadian rhythmicity by acute sleep deprivation leads to transient NSC overactivation and NSC pool exhaustion over time, which is effectively ameliorated by the inhibition of the LC NEergic neuronal activity or β3-adrenoceptors-mediated signaling. Finally, we demonstrate that NE/β3-adrenoceptors-mediated signaling regulates NSC activation through molecular clock BMAL1. Therefore, our study unravels that adult NSCs precisely coordinate circadian neural circuit and intrinsic molecular circadian clock to adapt their cellular behavior across the day.

The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut.

Adult stem cells are pivotal for maintaining tissue homeostasis, and their functional decline is linked to aging and its associated diseases, influenced by the niche cells' environment. Age- and cancer-related reduction of vitamin D and its receptor levels are well documented in human clinical studies. However, the mechanisms through which the vitamin D/vitamin D receptor pathway contributes to anti-aging and extends life expectancy are not well understood. In this study, we aimed to determine the protective role of the vitamin D/vitamin D receptor pathway in differentiated enterocytes (ECs) during intestinal stem cell (ISC) aging. By utilizing a well- established Drosophila midgut model for stem cell aging biology, we revealed that vitamin D receptor knockdown in ECs induced ISC proliferation, EC death, ISC aging, and enteroendocrine cell differentiation. Additionally, age- and oxidative stress-induced increases in ISC proliferation and centrosome amplification were reduced by vitamin D treatment. Our findings suggest a direct evidence of the anti-aging role of the vitamin D/vitamin D receptor pathway and provides insights into the molecular mechanisms underlying healthy aging in Drosophila.

Sirtuins Affect Cancer Stem Cells via Epigenetic Regulation of Autophagy.

Sirtuins (SIRTs) are stress-responsive proteins that regulate several post-translational modifications, partly by acetylation, deacetylation, and affecting DNA methylation. As a result, they significantly regulate several cellular processes. In essence, they prolong lifespan and control the occurrence of spontaneous tumor growth. Members of the SIRT family have the ability to govern embryonic, hematopoietic, and other adult stem cells in certain tissues and cell types in distinct ways. Likewise, they can have both pro-tumor and anti-tumor effects on cancer stem cells, contingent upon the specific tissue from which they originate. The impact of autophagy on cancer stem cells, which varies depending on the specific circumstances, is a very intricate phenomenon that has significant significance for clinical and therapeutic purposes. SIRTs exert an impact on the autophagy process, whereas autophagy reciprocally affects the activity of certain SIRTs. The mechanism behind this connection in cancer stem cells remains poorly understood. This review presents the latest findings that position SIRTs at the point where cancer cells and autophagy interact. Our objective is to highlight the various roles of distinct SIRTs in cancer stem cell-related functions through autophagy. This would demonstrate their significance in the genesis and recurrence of cancer and offer a more precise understanding of their treatment possibilities in relation to autophagy.

The nuclei of human adult stem cells can move within the cell and generate cellular protrusions to contact other cells

BackgroundThe neuronal transdifferentiation of adult bone marrow cells (BMCs) is still considered an artifact based on an alternative explanation of experimental results supporting this phenomenon obtained over decades. However, recent studies have shown that following neural induction, BMCs enter an intermediate cellular state before adopting neural-like morphologies by active neurite extension and that binucleated BMCs can be formed independent of any cell fusion events. These findings provide evidence to reject the idea that BMC neural transdifferentiation is merely an experimental artifact. Therefore, understanding the intermediate states that cells pass through during transdifferentiation is crucial given their potential application in regenerative medicine and disease modelling.MethodsIn this study, we examined the functional significance of the variety of morphologies and positioning that cell nuclei of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) can adopt during neural-like differentiation using live-cell nuclear fluorescence labelling, time-lapse microscopy, and confocal microscopy analysis.ResultsHere, we showed that after neural induction, hBM-MSCs enter an intermediate cellular state in which the nuclei are able to move within the cells, switching shapes and positioning and even generating cellular protrusions as they attempt to contact the cells around them. These findings suggest that changes in nuclear positioning occur because human cell nuclei somehow sense their environment. In addition, we showed the process of direct interactions between cell nuclei, which opens the possibility of a new level of intercellular interaction.ConclusionsThe present study advances the understanding of the intermediate stage through which hBM-MSCs pass during neural transdifferentiation, which may be crucial to understanding the mechanisms of these cell conversion processes and eventually harness them for use in regenerative medicine. Importantly, our study provides for the first time evidence that the nuclei of hBM-MSC-derived intermediate cells somehow sense their environment, generating cellular protrusions to contact other cells. In summary, human mesenchymal stromal cells could not only help to increase our understanding of the mechanisms underlying cellular plasticity but also facilitate the exact significance of nuclear positioning in cellular function and in tissue physiology.

Integrated Microfluidics for Single‐Cell Separation and On‐Chip Analysis: Novel Applications and Recent Advances

From deciphering infection and disease mechanisms to identifying novel biomarkers and personalizing treatments, the characteristics of individual cells can provide significant insights into a variety of biological processes and facilitate decision‐making in biomedical environments. Conventional single‐cell analysis methods are limited in terms of cost, contamination risks, sample volumes, analysis times, throughput, sensitivity, and selectivity. Although microfluidic approaches have been suggested as a low‐cost, information‐rich, and high‐throughput alternative to conventional single‐cell isolation and analysis methods, limitations such as necessary off‐chip sample pre‐ and post‐processing as well as systems designed for individual workflows have restricted their applications. In this review, a comprehensive overview of recent advances in integrated microfluidics for single‐cell isolation and on‐chip analysis in three prominent application domains are provided: investigation of somatic cells (particularly cancer and immune cells), stem cells, and microorganisms. Also, the use of conventional cell separation methods (e.g., dielectrophoresis) in unconventional or novel ways, which can advance the integration of multiple workflows in microfluidic systems, is discussed. Finally, a critical discussion related to current limitations of integrated microfluidic single‐cell workflows and how they could be overcome is provided.

The zinc finger protein CG12744 regulates intestinal stem cells in aged Drosophila through the EGFR and BMP pathways

AimAging is a process characterized by a time-dependent decline in the functionality of adult stem cells and is closely associated with age-related diseases. However, understanding how aging promotes disease and its underlying causes is critical for combating aging. Main methodsThe offspring of UAS-Gal4 and CG12744RNAiDrosophila were cultured for 33 days to evaluate the role of CG12744 in the aging intestine. Immunofluorescence was performed to detect specific cell type markers for assessing proliferation and differentiation. qRT–PCR was used to observe the changes in signaling regulating intestinal homeostasis in the aging intestine after CG12744 knockdown. 16S rRNA-seq analysis was also conducted to elucidate the role of gut microbes in CG12744-mediated intestinal dysfunction. Key findingsThe mRNA levels of CG12744 were significantly increased in the aged midguts. Knockdown of CG12744 in progenitor cells further exacerbates the age-related intestinal hyperplasia and dysfunction. In particular, upon depletion of CG12744 in progenitors, enteroblasts (EBs) exhibited an increased propensity to differentiate along the enteroendocrine cell (EE) lineage. In contrast, the overexpression of CG12744 in progenitor cells restrained age-related gut hyperplasia in Drosophila. Moreover, CG12744 prevented age-related intestinal stem cell (ISC) overproliferation and differentiation by modulating the EGFR, JNK, and BMP pathways. In addition, the inhibition of CG12744 resulted in a significant increase in the gut microbial composition in aging flies. SignificanceThis study established a role for the CG12744 in regulating the proliferation and differentiation of adult stem cells, thereby identifying a potential therapeutic target for diseases caused by age-related dysfunction stem cell dysfunction.

In-Vitro 3-Dimensional Organoid Models – A Concise Review on Clinical Importance

Organoids are three-dimensional structures that are grown in vitro. Adult stem cells, as well as embryonic stem cells and induced pluripotent stem cells, can be used to make them. To derive these organoids requirements are Tissue and Matrix. The matrix gives support and it should resemble the extracellular matrix for the cells. Microcontact printing and Bioprinting techniques are used for preparing matrices. Many organoids are generated from cells like brain organoids, liver organoids, mammary gland organoids, and some cancer organoids. These Organoid models are used for studying the human-specific disease mechanisms. Due to the specific organoid models, study of many tissues is possible ranging from small intestine, prostate, brain and liver. This review explores the applications of cell-derived organoids, their advantages, and current breakthroughs in organoid models.

Invasive Fungal Infections Are Rare in Pediatric and Young Adult Autologous Hematopoietic Stem Cell Transplant Patients

Invasive Fungal Infections Are Rare in Pediatric and Young Adult Autologous Hematopoietic Stem Cell Transplant Patients

Modulation of Inflammation By Unrestricted Somatic Stem Cells (USSCs) to Suppress Fibrosis in Mice with Dystrophic Epidermolysis Bullosa

Modulation of Inflammation By Unrestricted Somatic Stem Cells (USSCs) to Suppress Fibrosis in Mice with Dystrophic Epidermolysis Bullosa