Stem Cell Quiescence versus Senescence: The Key for Healthy Aging

BACKGROUND: Aging tissues lose their homeostatic and regenerative capacities, which has been linked to the degeneration of the stem cells such as the tissue-specific stem cells, the stem cell niches, and systemic cues that regulate stem cell activity.CONTENT: The maintenance of tissue homeostatic and regeneration dependent on its tissue-specific stem cells, that —long-lived cells with the ability to self-renew and differentiate into mature cells. Understanding the molecular mechanisms that governs stem cell survival, self-renewal, quiescence, proliferation, and commitment to specific differentiated cell lineages is critical for identifying the drivers and effectors of age-associated stem cell failure. Such understanding will be critical for the development of therapeutic approaches that can decrease, and possibly reverse and repair the age-related degenerative process in aging tissues.SUMMARY: The exact mechanisms and reasons of aging process were not fully elucidated until now. Stem cells is one of the keys for maintaining tissues heath and understanding how stem cell decline with age will give us opportunities to find strategy in increasing somatic stem cells regenerative capacity and delay the aging process.KEYWORDS: adult stem cell, aging, epigenetic, metabolism, quiescence, senescence

Airway Basal Cells, Protectors of Epithelial Walls in Health and Respiratory Diseases

The airway epithelium provides a critical barrier to the outside environment. When its integrity is impaired, epithelial cells and residing immune cells collaborate to exclude pathogens and to heal tissue damage. Healing is achieved through tissue-specific stem cells: the airway basal cells. Positioned near the basal membrane, airway basal cells sense and respond to changes in tissue health by initiating a pro-inflammatory response and tissue repair via complex crosstalks with nearby fibroblasts and specialized immune cells. In addition, basal cells have the capacity to learn from previous encounters with the environment. Inflammation can indeed imprint a certain memory on basal cells by epigenetic changes so that sensitized tissues may respond differently to future assaults and the epithelium becomes better equipped to respond faster and more robustly to barrier defects. This memory can, however, be lost in diseased states. In this review, we discuss airway basal cells in respiratory diseases, the communication network between airway basal cells and tissue-resident and/or recruited immune cells, and how basal cell adaptation to environmental triggers occurs.

Germline competent mesoderm: the substrate for vertebrate germline and somatic stem cells?

ABSTRACT In vitro production of tissue-specific stem cells [e.g. haematopoietic stem cells (HSCs)] is a key goal of regenerative medicine. However, recent efforts to produce fully functional tissue-specific stem cells have fallen short. One possible cause of shortcomings may be that model organisms used to characterize basic vertebrate embryology (Xenopus, zebrafish, chick) may employ molecular mechanisms for stem cell specification that are not conserved in humans, a prominent example being the specification of primordial germ cells (PGCs). Germ plasm irreversibly specifies PGCs in many models; however, it is not conserved in humans, which produce PGCs from tissue termed germline-competent mesoderm (GLCM). GLCM is not conserved in organisms containing germ plasm, or even in mice, but understanding its developmental potential could unlock successful production of other stem cell types. GLCM was first discovered in embryos from the axolotl and its conservation has since been demonstrated in pigs, which develop from a flat-disc embryo like humans. Together these findings suggest that GLCM is a conserved basal trait of vertebrate embryos. Moreover, the immortal nature of germ cells suggests that immortality is retained during GLCM specification; here we suggest that the demonstrated pluripotency of GLCM accounts for retention of immortality in somatic stem cell types as well. This article has an associated Future Leaders to Watch interview with the author of the paper.

5. Tissue-specific stem cells

‘Tissue-specific stem cells’ explores tissue-specific stem cells, which are stem cells found in the postnatal body that are responsible for tissue renewal or for repair following damage. Tissue-specific stem cells share with pluripotent stem cells the same ability to persist indefinitely as a population, to reproduce themselves, and to generate differentiated progeny cells. However, tissue-specific stem cells share few molecular characteristics with embryonic stem (ES) cells or induced pluripotent stem cells (iPS cells), such as expression of specific transcription factors or cell surface molecules. Only renewal tissues have stem cells in the sense of a special population of cells that reproduce themselves and continue to generate differentiated progeny.

6. Therapy using tissue-specific stem cells

‘Therapy using tissue-specific stem cells’ begins with haematopoietic stem cell transplantation (HSCT), which is considered the most important type of stem cell therapy. HSCT covers the transplantation of bone marrow and other types of transplant where the blood-forming stem cells of the graft come from non-marrow sources. It is used mostly for the treatment of leukaemias and lymphomas. Some genetic diseases of the blood have also been successfully treated using allogeneic HSCT. There are also other examples of cell therapy using tissue-specific stem cells, such as epidermal cells for the treatment of burns and limbal (corneal) stem cells for treatment of eye injuries.

Induced Tissue-Specific Stem Cells (iTSCs): Their Generation and Possible Use in Regenerative Medicine

Induced tissue-specific stem cells (iTSCs) are partially reprogrammed cells which have an intermediate state, such as progenitors or stem cells. They originate from the de-differentiation of differentiated somatic cells into pluripotent stem cells, such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), or from the differentiation of undifferentiated cells. They show a limited capacity to differentiate and a morphology similar to that of somatic cell stem cells present in tissues, but distinct from that of iPSCs and ESCs. iTSCs can be generally obtained 7 to 10 days after reprogramming of somatic cells with Yamanaka’s factors, and their fibroblast-like morphology remains unaltered. iTSCs can also be obtained directly from iPSCs cultured under conditions allowing cellular differentiation. In this case, to effectively induce iTSCs, additional treatment is required, as exemplified by the conversion of iPSCs into naïve iPSCs. iTSCs can proliferate continuously in vitro, but when transplanted into immunocompromised mice, they fail to generate solid tumors (teratomas), implying loss of tumorigenic potential. The low tendency of iTSCs to elicit tumors is beneficial, especially considering applications for regenerative medicine in humans. Several iTSC types have been identified, including iTS-L, iTS-P, and iTS-D, obtained by reprogramming hepatocytes, pancreatic cells, and deciduous tooth-derived dental pulp cells, respectively. This review provides a brief overview of iPSCs and discusses recent advances in the establishment of iTSCs and their possible applications in regenerative medicine.

Evaluation of exosome derivatives as bio-informational reprogramming therapy for cancer

Exosomes are nanoparticle sized (100 ± 50 nm) extracellular vesicles (ECVs) that play important roles in cell-to-cell communication. They do this by utilizing their natural ability to shuttle signaling molecules across the cellular microenvironment and promote paracrine signaling. Currently, exosomes are being explored for their potential as therapeutic agents for various degenerative diseases including cancer. The rationale behind their therapeutic ability is that they can transfer signaling biomolecules, and subsequently induce metabolic and physiological changes in diseased cells and tissues. In addition, exosomes can be used as a drug delivery system and may be very effective at reducing toxicity and increasing bioavailability of therapeutic molecules and drugs. Although exosomes were first believed to be a waste product of the cell, current research has demonstrated that these particles can serve as modulators of the immune system, act as cancer biomarkers, cause re-differentiation of cancer cells, and induce apoptosis in diseased cells. Extensive research has been performed specifically using amniotic fluid-derived extracellular vesicles, named “cytosomes”. While the use of cytosomes in clinical application is still in the early stages, researchers have shown great potential for these EVs in regenerative medicine as immune modulators, in controlling microbial infection and by inducing tissue repair through the activation of endogenous, tissue-specific stem cells. This review emphasizes the capabilities of specific subsets of extracellular vesicles that can potentially be used for cancer therapy, principally as a source of bi-informational reprogramming for malignant cells.

Stem Cells: The Future Promise of Stem Cells in Healthspan

Tissue specific stem cells are critical for maintenance and repair of tissues and organs throughout life. However, during aging, the functionality of stem cells declines, contributing to tissue decline. This symposium will focus on the mechanisms underlying stem cell aging in various compartments, including muscle, brain and the hematopoietic system.

Molecular and Morphological Signatures of Chordate Development: Two Distinct Pathways, One Tunicate

SummaryAll chordates, including urochordates such as tunicates, develop through embryogenesis. The chordate larvae of colonial tunicates metamorphose to lose all chordate structures such as notochord, neural tube, segmented musculature, and then develop by asexual reproduction [blastogenesis], whereby stem cells form tissues and organs. These two developmental pathways establish the same body axis, morphogenetic patterning and organ formation. It is unknown if this convergent morphology implies convergent cellular and molecular mechanisms, and whether the stem cells that mediate these processes differ. Using the colonial tunicate Botryllus schlosseri, we combined transcriptome sequencing and multiple microscopy techniques to study the molecular and morphological signatures of cells at each developmental stage of embryogenesis and blastogenesis. This revealed that the molecular programs are distinct, but the blastogenic tissue-specific stem cells and embryonic precursor populations share similar molecular profiles. By comparing embryogenesis in other chordates we found shared developmental principles, highlighting transcription factors as key evolutionary conserved elements. This study establishes a platform for advancing the science of stem cell biology and regulation of development and regeneration.