scholarly journals Healthy ageing and spermatogenesis

Reproduction ◽  
2021 ◽  
Vol 161 (4) ◽  
pp. R89-R101
Author(s):  
Eva Pohl ◽  
Jörg Gromoll ◽  
Joachim Wistuba ◽  
Sandra Laurentino
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Current Knowledge ◽  
Hormone Secretion ◽  
Healthy Ageing ◽  
Hormone Production ◽  
Male Germ Cells ◽  
Cell Niche ◽  
Stem Cell Populations ◽  
The Impact

Delayed family planning and increased parental age increase the risk for infertility and impaired offspring health. While the impact of ageing on oogenesis is well studied, this is less understood on spermatogenesis. Assessing ageing effects on the male germline presents a challenge in differentiating between the effects of ageing-associated morbidities, infertility and ‘pure’ ageing. However, understanding the impact of ageing on male germ cells requires the separation of age from other factors. In this review, we therefore discuss the current knowledge on healthy ageing and spermatogenesis. Male ageing has been previously associated with declining sperm parameters, disrupted hormone secretion and increased time-to-pregnancy, among others. However, recent data show that healthy ageing does not deteriorate testicular function in terms of hormone production and spermatogenic output. In addition, intrinsic, age-dependent, highly specific processes occur in ageing germ cells that are clearly distinct from somatic ageing. Changes in spermatogonial stem cell populations indicate compensation for stem cell exhaustion. Alterations in the stem cell niche and molecular ageing signatures in sperm can be observed in ageing fertile men. DNA fragmentation rates as well as changes in DNA methylation patterns and increased telomere length are hallmarks of ageing sperm. Taken together, we propose a putative link between the re-activation of quiescent Adark spermatogonia and molecular changes in aged sperm descending from these activated spermatogonia. We suggest a baseline of ‘pure' age effects in male germ cells which can be used for subsequent studies in which the impact of infertility or co-morbidities will be studied.

scholarly journals The 28 + 28 day design is an effective sampling time for analyzing mutant frequencies in rapidly proliferating tissues of MutaMouse animals

2021 ◽  
Vol 95 (3) ◽  
pp. 1103-1116
Author(s):  
Francesco Marchetti ◽  
Gu Zhou ◽  
Danielle LeBlanc ◽  
Paul A. White ◽  
Andrew Williams ◽  
...  
Keyword(s):  
Germ Cells ◽  
False Negative ◽  
Sampling Time ◽  
Male Germ Cells ◽  
Negative Results ◽  
False Negative Results ◽  
Detection Of Mutations ◽  
The Impact ◽  
Sampling Times

AbstractThe Organisation for Economic Co-Operation and Development Test Guideline 488 (TG 488) uses transgenic rodent models to generate in vivo mutagenesis data for regulatory submission. The recommended design in TG 488, 28 consecutive daily exposures with tissue sampling three days later (28 + 3d), is optimized for rapidly proliferating tissues such as bone marrow (BM). A sampling time of 28 days (28 + 28d) is considered more appropriate for slowly proliferating tissues (e.g., liver) and male germ cells. We evaluated the impact of the sampling time on mutant frequencies (MF) in the BM of MutaMouse males exposed for 28 days to benzo[a]pyrene (BaP), procarbazine (PRC), isopropyl methanesulfonate (iPMS), or triethylenemelamine (TEM) in dose–response studies. BM samples were collected + 3d, + 28d, + 42d or + 70d post exposure and MF quantified using the lacZ assay. All chemicals significantly increased MF with maximum fold increases at 28 + 3d of 162.9, 6.6, 4.7 and 2.8 for BaP, PRC, iPMS and TEM, respectively. MF were relatively stable over the time period investigated, although they were significantly increased only at 28 + 3d and 28 + 28d for TEM. Benchmark dose (BMD) modelling generated overlapping BMD confidence intervals among the four sampling times for each chemical. These results demonstrate that the sampling time does not affect the detection of mutations for strong mutagens. However, for mutagens that produce small increases in MF, sampling times greater than 28 days may produce false-negative results. Thus, the 28 + 28d protocol represents a unifying protocol for simultaneously assessing mutations in rapidly and slowly proliferating somatic tissues and male germ cells.

scholarly journals Review of the Current Knowledge on the Role of Stem Cell Transplantation in Neurorehabilitation

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Anna M. Kamelska-Sadowska ◽  
Joanna Wojtkiewicz ◽  
Ireneusz M. Kowalski
Keyword(s):  
Stem Cell ◽  
Current Knowledge ◽  
Rehabilitation Program ◽  
Convincing Evidence ◽  
Hind Limbs ◽  
Neurologic Disorders ◽  
Cord Injury ◽  
Rehabilitation Protocols ◽  
Simultaneous Use ◽  
The Impact

The management involving stem cell (SC) therapy along with physiotherapy offers tremendous chance for patients after spinal cord injury (SCI), traumatic brain injury (TBI), stroke, etc. However, there are still only a limited number of reports assessing the impact of stem cells (SCs) on the rehabilitation process and/or the results of the simultaneous use of SC and rehabilitation. Additionally, since there is still not enough convincing evidence about the effect of SCT on humans, e.g., in stroke, there have been no studies conducted concerning rehabilitation program formation and expected outcomes. It has been shown that bone marrow-derived mesenchymal stem cell (BMSCs) transplantation in rats combined with hyperbaric oxygen therapy (HBO) can promote the functional recovery of hind limbs after SCI. An anti-inflammatory effect has been shown. One case study showed that, after the simultaneous use of SCT and rehabilitation, an SCI patient progressed from ASIA Grade A to ASIA Grade C. Such promising data in the case of complete tetraplegia could be a breakthrough in the treatment of neurologic disorders in humans. Although SCT appears as a promising method for the treatment of neurological conditions, e.g., complete tetraplegia, much work should be done towards the development of rehabilitation protocols.

Oxygen Availability and Stem Cells: Impact On Development and Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-37-SCI-37
Author(s):  
M. Celeste Simon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Conflicts Of Interest ◽  
Hypoxia Inducible Factor ◽  
Stem And Progenitor Cells ◽  
Adult Hippocampus ◽  
Underlying Mechanisms ◽  
Stem Cell Populations ◽  
The Impact

Abstract Abstract SCI-37 Stem and progenitor cells reside in specialized microenvironments that regulate their function. While some stem/progenitor cells are perivascular, others clearly occupy hypoxic niches and may be regulated by O2 gradients. We are currently evaluating underlying mechanisms for the impact of O2 levels on stem and progenitor cells within distinct microenvironments. We have previously shown that neural stem cells within the adult hippocampus are closely associated with low O2 regions and that hypoxia-inducible factor 1α (HIF-1α), a principle mediator of hypoxic adaptations, modulates Wnt-β catenin signaling to maintain stem cell proliferation, differentiation, and neuronal maturation. We have extended these findings to other stem cell populations, such as those of adult muscle and bone marrow. Our findings will be presented at this meeting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Transforming Growth Factor-Beta Signaling in the Neural Stem Cell Niche: A Therapeutic Target for Huntington's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Mahesh Kandasamy ◽  
Ralf Reilmann ◽  
Jürgen Winkler ◽  
Ulrich Bogdahn ◽  
Ludwig Aigner
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Transforming Growth Factor Beta ◽  
Stem Cell Niche ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
Adult Brain ◽  
Therapeutic Concept ◽  
Neural Stem Cell Niche ◽  
Cell Niche

The neural stem cell niches possess the regenerative capacity to generate new functional neurons in the adult brain, suggesting the possibility of endogenous neuronal replacement after injury or disease. Huntington disease (HD) is a neurodegenerative disease and characterized by neuronal loss in the basal ganglia, leading to motor, cognitive, and psychological disabilities. Apparently, in order to make use of the neural stem cell niche as a therapeutic concept for repair strategies in HD, it is important to understand the cellular and molecular composition of the neural stem cell niche under such neurodegenerative conditions. This paper mainly discusses the current knowledge on the regulation of the hippocampal neural stem cell niche in the adult brain and by which mechanism it might be compromised in the case of HD.

Male germ line stem cells: from cell biology to cell therapy

2003 ◽  
Vol 15 (6) ◽  
pp. 323 ◽  
Author(s):  
David Pei-Cheng Lin ◽  
Ming-Yu Chang ◽  
Bo-Yie Chen ◽  
Han-Hsin Chang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Germ Cells ◽  
Germ Line ◽  
Current Status ◽  
Seminiferous Tubules ◽  
Male Germ Line ◽  
Male Germ Cells ◽  
Stem Cell Lines

Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has gradually facilitated research into spermatogenesis and male infertility, to an extent beyond that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. The present review concentrates on the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines.

scholarly journals Between Fate Choice and Self-Renewal—Heterogeneity of Adult Neural Crest-Derived Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Anna L. Höving ◽  
Beatrice A. Windmöller ◽  
Cornelius Knabbe ◽  
Barbara Kaltschmidt ◽  
Christian Kaltschmidt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Crest ◽  
Current Knowledge ◽  
Mapk Signaling ◽  
Cellular Heterogeneity ◽  
Self Renewal ◽  
The Impact

Stem cells of the neural crest (NC) vitally participate to embryonic development, but also remain in distinct niches as quiescent neural crest-derived stem cell (NCSC) pools into adulthood. Although NCSC-populations share a high capacity for self-renewal and differentiation resulting in promising preclinical applications within the last two decades, inter- and intrapopulational differences exist in terms of their expression signatures and regenerative capability. Differentiation and self-renewal of stem cells in developmental and regenerative contexts are partially regulated by the niche or culture condition and further influenced by single cell decision processes, making cell-to-cell variation and heterogeneity critical for understanding adult stem cell populations. The present review summarizes current knowledge of the cellular heterogeneity within NCSC-populations located in distinct craniofacial and trunk niches including the nasal cavity, olfactory bulb, oral tissues or skin. We shed light on the impact of intrapopulational heterogeneity on fate specifications and plasticity of NCSCs in their niches in vivo as well as during in vitro culture. We further discuss underlying molecular regulators determining fate specifications of NCSCs, suggesting a regulatory network including NF-κB and NC-related transcription factors like SLUG and SOX9 accompanied by Wnt- and MAPK-signaling to orchestrate NCSC stemness and differentiation. In summary, adult NCSCs show a broad heterogeneity on the level of the donor and the donors’ sex, the cell population and the single stem cell directly impacting their differentiation capability and fate choices in vivo and in vitro. The findings discussed here emphasize heterogeneity of NCSCs as a crucial parameter for understanding their role in tissue homeostasis and regeneration and for improving their applicability in regenerative medicine.

Novel 3D-Model for the Hematopoietic Stem Cell Niche Using MSC in a KITChip Based Bioreactor

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1331-1331
Author(s):  
Patrick Wuchter ◽  
Rainer Saffrich ◽  
Stefan Giselbrecht ◽  
Anthony D. Ho ◽  
Eric Gottwald
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Niche ◽  
Culture Period ◽  
Circulation System ◽  
Beta Catenin ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche ◽  
Cell Niche ◽  
The Impact

Abstract Abstract 1331 Human mesenchymal stromal cells (MSC) maintain “stemness” of human hematopoietic stem cells (HSC) by cell-cell contact when used as feeder-layer. We previously demonstrated the presence of specific cadherin-catenin-based junctions between HSC and MSC in a two-dimensional coculture-setting. To develop a more physiological in vitro model for the hematopoietic stem cell niche, we have established a novel 3D-coculture-system based on the so-called 3D-KITChip capable of accommodating up to 1×107 MSC on an area of ∼2cm2. For a precise reproduction of the microenvironment of the niche, the 3D-KITChip is inserted in a microfluidic bioreactor, allowing active nutrient and gas supply. MSC were derived from bone marrow aspirates of healthy voluntary donors and grown to confluence following standard protocols. MSC were then trypsinized and reseeded (3×105 cells) on a unique microchip with defined microwell cavities, developed by the Karlsruhe Institute of Technology (“3D-KITChip”). After 48–72h, 2×105 HSC isolated from umbilical cord blood were added and the chip was inserted in a microfluidic bioreactor. The closed circulation system comprising the bioreactor, a cassette pump, and a medium reservoir was run for up to 7 days. In this closed loop setup, oxygen concentration, medium composition and medium flow could be controlled precisely. After 1–7d of coculture, the bioreactor was re-opened and the two cell populations were analyzed by immunostaining, RT2-PCR, genomics and functional assays such as colony forming assays (CFA). The MSC form a complex 3D mesh in the microcavities of the 3D-KITChip which is very stable for the time of the experiments and could be cultured in this way for up to 6 weeks. It could be demonstrated that HSC are distributed three dimensionally inside this MSC mesh. HSC could be kept alive in this environment for at least 7 days and a defined proportion of CD34+-HSC adhered to the MSC in the microcavities and built up direct cellular connections to the surrounding MSC. A direct comparison of the adhering vs. the non-adhering cell-fraction is currently underway. By means of RT2-PCR, we could demonstrate that the proportion of CD34+/nestin+/p21+/CXCR4+ cells could be maintained throughout the whole culture period of 7 days. Moreover, no CD38 or CD44-expression could be detected, whereas c-kit-expression continuously decreased during the culture period. This novel setup allows the precise adjustment of the key elements in the hematopoietic stem cell niche that govern stem cell homing, engraftment and mobilization. Further experiments aim to elucidate the role of the 3D-environment, oxygen tension, sheer stress, composition of the medium and perfusion conditions on the above mentioned stem cell behavior. The impact of junctional complexes comprising alpha-/beta-catenin, p120 and N-cadherin in this context will be determined. Disclosures: Ho: Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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