Role Of Stem Cell Niche Research Articles

Changes in Stem Cell Regulation and Epithelial Organisation during Carcinogenesis and Disease Progression in Gynaecological Malignancies.

Simple SummaryRecent advances in our understanding of the stem cell potential in adult tissues have far-reaching implications for cancer research, and this creates new opportunities for the development of new therapeutic strategies. Here we outline changes in stem cell biology that characterize main gynaecological malignancies, ovarian, endometrial, and cervical cancer, and focus on specific differences between them. We highlight the importance of the local niche environment as a driver of malignant transformation in addition to mutations in key cancer-driving genes. Patient-derived organoids capture in vitro main aspects of cancer tissue architecture and stemness regulatory mechanisms, thus providing a valuable new platform for a personalized approach in the treatment of gynecological malignancies. This review summarizes the main achievement and formulates remaining open questions in this fast-evolving research field.Gynaecological malignancies represent a heterogeneous group of neoplasms with vastly different aetiology, risk factors, molecular drivers, and disease outcomes. From HPV-driven cervical cancer where early screening and molecular diagnostics efficiently reduced the number of advanced-stage diagnosis, prevalent and relatively well-treated endometrial cancers, to highly aggressive and mostly lethal high-grade serous ovarian cancer, malignancies of the female genital tract have unique presentations and distinct cell biology features. Recent discoveries of stem cell regulatory mechanisms, development of organoid cultures, and NGS analysis have provided valuable insights into the basic biology of these cancers that could help advance new-targeted therapeutic approaches. This review revisits new findings on stemness and differentiation, considering main challenges and open questions. We focus on the role of stem cell niche and tumour microenvironment in early and metastatic stages of the disease progression and highlight the potential of patient-derived organoid models to study key events in tumour evolution, the appearance of resistance mechanisms, and as screening tools to enable personalisation of drug treatments.

Role of the stem cell niche in the pathogenesis of epithelial ovarian cancers

Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. Recent extensive genomic analyses of epithelial ovarian cancer (EOC), particularly the most common and deadly form of high-grade serous ovarian carcinoma, have provided important insights into the repertoire of molecular aberrations that are characteristic for this malignancy. However, interpretation of the discovered aberrations is complicated because the origin and mechanisms of progression of EOC remain uncertain. Here, we summarize current views on the cell of origin of EOC and discuss recent findings of a cancer-prone stem cell niche for ovarian surface epithelium, one of the major likely sources of EOC. We also outline future directions and challenges in studying the role of stem cell niches in EOC pathogenesis.

Stem cell delivery systems inspired by tissue-specific niches.

Since stem cells have the capacity to differentiate into a variety of cell types, stem cell delivery systems (SCDSs) can be effective therapeutic strategies for a multitude of diseases and disorders. For stem cell-based therapy, stem cells are introduced directly (or peripherally) into a target tissue via different delivery systems. Despite initial promising results obtained from preclinical studies, a number of technical hurdles must be overcome for ultimate clinical utility of stem cells. A key aspect of SCDSs is how to create local environments, called stem cell niches, for improvement of survival and engraftment as well as the fate of transplanted stem cells. The stem cell niches encompassing a wide range of biochemical, biophysical, and biomechanical cues play a guidance role to modulate stem cell behaviors such as adhesion, proliferation, and differentiation. Recent studies have tried to decipher the complex interplay between stem cells and niches, and thereafter to engineer SCDS, mimicking dynamic stem cell niches encompassing a wide range of biochemical, biophysical, and biomechanical cues. Here, we discuss the biological role of stem cell niches and highlight recent progress in SCDS to mimic stem cell niches, particularly focusing on important biomaterial properties for modulating stem cell fate.

Introducing the 2014 JALA Ten Honorees

Introducing the 2014 JALA Ten Honorees

Extracellular Matrix is an Important Component of Limbal Stem Cell Niche.

Extracellular matrix plays an important role in stem cell niche which maintains the undifferentiated stem cell phenotype. Human corneal epithelial stem cells are presumed to reside mainly at the limbal basal epithelium. Efforts have been made to characterize different components of the extracellular matrix that are preferentially expressed at the limbus. Mounting evidence from experimental data suggest that these components are part of the stem cell niche and play a role in the homeostasis of limbal stem cells. The extracellular matrix provides a mechanical and structural support as well as regulates cellular functions such as adhesion, migration, proliferation, self-renewal and differentiation. Optimization of the extracellular matrix components might be able to recreate an ex vivo stem cell niche to expand limbal stem cells.

Pretransplant Parathyroid Hormone Level Has No Correlation with Platelet Recovery After Stem Cell

AbstractAbstract 4495 BackgroundStem cell fate is influenced by specialized microenvironments called as stem cell niche. Osteoblasts are considerd to play very important role in stem cell niche. They are activated by parathyroid hormone (PTH) or PTH related protein through PTH/PTHrP receptor and produce hematopoietic growth factors. In few large animal studies PTH treatment after hematopoietic stem cell transplantation (HSCT) improved post-transplant platelet count and CD4 lymphocyte count. Effect of PTH on cord blood stem cell transplantation to improve engraftment is under clinical trial. Therefore, authors investigated on correlation between pre-transplant serum PTH level and platelet recovery after allogeneic HSCT. MethodsFrom January 2008 to December 2009, we measured pre-transplant serum PTH, ferritin of 28 patients who underwent allogeneic HSCT. Post-transplant platelet was checked at the point of post-transplant 14 days, 30 days, 60 days, 90 days and 180days. Surveillance of cytomegalovirus was done by weekly or biweekly CMV-PCR assay. Acute graft-versus-host disease (GVHD) was graded by IBMTR classification and chronic GVHD by NIH scoring system. ResultsFive patients received graft from partially matched donors and the others from fully matched donors, 15 from unrelated and 13 from related donors. Nineteen patients were in high risk at diagnosis. Nonmyeloablative conditioning was applied to 7 patients. Only 1 patient used bone marrow as stem cell source. Median dose of infused stem cell was 5.7×10∧6/kg (range 1.68 – 12.74). All patients were successfully engrafted. Acute GVHD more than grade 2 occurred in 15, and chronic GVHD more than moderate degree in 7. Five patients relapsed and 15 patients died of relapse or treatment related mortality. Pre-transplant serum PTH had no correlation with platelet count recovery. There was no correlation with pre-HSCT PTH and acute or chronic GVHD. However patient with lower PTH level had tendency to more frequent CMV reactivation (P=0.098). ConclusionOur hypothesis was that higher pre-transplant PTH would be related to better platelet recovery but failed to find correlation between two of them. There are various factors which affect engraftment and graft function. Role of PTH for engraftment should be evaluated in larger number of cases. Disclosures:No relevant conflicts of interest to declare.

MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM: Extracellular matrix in skeletal muscle development and meat quality1

MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM: Extracellular matrix in skeletal muscle development and meat quality1

Stem cell niches and endogenous electric fields in tissue repair

Adult stem cells are responsible for homeostasis and repair of many tissues. Endogenous adult stem cells reside in certain regions of organs, known as the stem cell niche, which is recognized to have an important role in regulating tissue maintenance and repair. In wound healing and tissue repair, stem cells are mobilized and recruited to the site of wound, and participate in the repair process. Many regulatory factors are involved in the stem cell-based repair process, including stem cell niches and endogenous wound electric fields, which are present at wound tissues and proved to be important in guiding wound healing. Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair, and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.

Role of stem cell niche in body aging processes

Replacement of damaged differentiated cells by new cells due to the asymmetric division of stem cells can provide unlimited tolerance to degeneration of human tissues, if multipotent cells themselves are “immortal.” However, stem cells exist in a particular microenvironment (stem cell niche) and feel their negative impact with age, which attenuates the proliferate capacity of stem cells and leads to incorrect differentiation or, instead, uncontrolled division (promotion of tumor genesis). As a result, stem cell injection to elder persons will be not efficient, because “young” stem cell will engraft to the “old” niche. To sufficient increasing of lifespan, it is necessary to modify stem niche signals by injection of an additional quantity of required growth factors in well-defined proportions.

Role of Stem Cell Niche in the Maintenance of Hematopoietic Stem Cells

The quiescent state in the cell cycle is thought to be indispensable for the maintenance of hematopoietic stem cells (HSCs). The interaction between HSCs and their niche is critical for maintaining the stem cell properties of HSCs, including self-renewal capacity and the ability of differentiation into single or multiple lineages. The niche cells produce signaling molecules, extracellular matrix, and cell adhesion molecules, and regulate stem cell fates. HSCs balance quiescence and cell division in the stem cell niche for long-term sustaining of hematopoiesis in the niche. Recently, long-term repopulating (LT)-HSCs exist frequently in endosteal surface of trabecular bone area in bone marrow (BM), and it was clarified that an osteoblastic cells function as a niche cells for HSCs. The specific properties of HSC are dynamically controlled by the signalings of receptor/ligand and cell adhesion molecules produced by osteoblastic cells.We have recently reported that side-population (SP) cells in HSCs are in the quiescent state of cell cycle. Cell adhesion of HSCs to the osteoblastic niche enhanced the ability of HSCs to become quiescent, resulting in protection of the HSC compartment from stresses suppressing hematopoiesis.

Asymmetry of stem cell fate and the potential impact of the niche

Asymmetric cell division is a common concept to explain the capability of stem cells to simultaneously produce a continuous output of differentiated cells and to maintain their own population of undifferentiated cells. Whereas for some stem cell systems, an asymmetry in the division process has explicitly been demonstrated, no evidence for such a functional asymmetry has been shown for hematopoietic stem cells (HSC) so far. This raises the question regarding whether asymmetry of cell division is a prerequisite to explain obvious heterogeneity in the cellular fate of HSC. Through the application of a mathematical model based on self-organizing principles, we demonstrate that the assumption of asymmetric stem cell division is not necessary to provide a consistent account for experimentally observed asymmetries in the development of HSC. Our simulation results show that asymmetric cell fate can alternatively be explained by a reversible expression of functional stem cell potentials, controlled by changing cell-cell and cell-microenvironment interactions. The proposed view on stem cell organization is pointing to the potential role of stem cell niches as specific signaling environments, which induce developmental asymmetries and therefore, generate cell fate heterogeneity. The self-organizing concept is fully consistent with the functional definition of tissue stem cells. It naturally includes plasticity phenomena without contradicting a hierarchical appearance of the stem cell population. The concept implies that stem cell fate is only predictable in a probabilistic sense and that retrospective categorization of stem cell potential, based on individual cellular fates, provides an incomplete picture.