scholarly journals The Fountain of Youth: A tale of parabiosis, stem cells, and rejuvenation

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 376-383 ◽  
Author(s):  
Massimo Conese ◽  
Annalucia Carbone ◽  
Elisa Beccia ◽  
Antonella Angiolillo

AbstractTransfusion (or drinking) of blood or of its components has been thought as a rejuvenation method since ancient times. Parabiosis, the procedure of joining two animals so that they share each others blood circulation, has revitalized the concept of blood as a putative drug. Since 2005, a number of papers have reported the anti-ageing effect of heterochronic parabiosis, which is joining an aged mouse to a young partner. The hallmark of aging is the decline of regenerative properties in most tissues, partially attributed to impaired function of stem and progenitor cells. In the parabiosis experiments, it was elegantly shown that factors derived from the young systemic environment are able to activate molecular signaling pathways in hepatic, muscle or neural stem cells of the old parabiont leading to increased tissue regeneration. Eventually, further studies have brought to identify some soluble factors in part responsible for these rejuvenating effects, including the chemokine CCL11, the growth differentiation factor 11, a member of the TGF-β superfamily, and oxytocin. The question about giving whole blood or specific factors in helping rejuvenation is open, as well as the mechanisms of action of these factors, deserving further studies to be translated into the life of (old) human beings.

2021 ◽  
Vol 11 (2) ◽  
pp. 172
Author(s):  
Arrin C. Brooks ◽  
Brandon J. Henderson

While various modalities of chronic nicotine use have been associated with numerous negative consequences to human health, one possible benefit of nicotine exposure has been uncovered. The discovery of an inverse correlation between smoking and Parkinson’s disease, and later Alzheimer’s disease as well, motivated investigation of nicotine as a neuroprotective agent. Some studies have demonstrated that nicotine elicits improvements in cognitive function. The hippocampus, along with the subventricular zone (SVZ), is a distinct brain region that allow for ongoing postnatal neurogenesis throughout adulthood and plays a major role in certain cognitive behaviors like learning and memory. Therefore, one hypothesis underlying nicotine-induced neuroprotection is possible effects on neural stem cells and neural precursor cells. On the other hand, nicotine withdrawal frequently leads to cognitive impairments, particularly in hippocampal-dependent behaviors, possibly suggesting an impairment of hippocampal neurogenesis with nicotine exposure. This review discusses the current body of evidence on nicotine’s effects on neural stem cells and neural progenitors. Changes in neural stem cell proliferation, survival, intracellular dynamics, and differentiation following acute and chronic nicotine exposure are examined.


Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2029
Author(s):  
Luis Gustavo Saboia Ponte ◽  
Isadora Carolina Betim Pavan ◽  
Mariana Camargo Silva Mancini ◽  
Luiz Guilherme Salvino da Silva ◽  
Ana Paula Morelli ◽  
...  

Flavonoids represent an important group of bioactive compounds derived from plant-based foods and beverages with known biological activity in cells. From the modulation of inflammation to the inhibition of cell proliferation, flavonoids have been described as important therapeutic adjuvants against several diseases, including diabetes, arteriosclerosis, neurological disorders, and cancer. Cancer is a complex and multifactor disease that has been studied for years however, its prevention is still one of the best known and efficient factors impacting the epidemiology of the disease. In the molecular and cellular context, some of the mechanisms underlying the oncogenesis and the progression of the disease are understood, known as the hallmarks of cancer. In this text, we review important molecular signaling pathways, including inflammation, immunity, redox metabolism, cell growth, autophagy, apoptosis, and cell cycle, and analyze the known mechanisms of action of flavonoids in cancer. The current literature provides enough evidence supporting that flavonoids may be important adjuvants in cancer therapy, highlighting the importance of healthy and balanced diets to prevent the onset and progression of the disease.


2008 ◽  
Vol 140 (6) ◽  
pp. 673-681 ◽  
Author(s):  
Joel C. Wojciechowski ◽  
Srinivas D. Narasipura ◽  
Nichola Charles ◽  
Deanne Mickelsen ◽  
Kuldeeepsinh Rana ◽  
...  

Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.


2017 ◽  
Vol 4 (4) ◽  
pp. 533-542 ◽  
Author(s):  
Guangdun Peng ◽  
Patrick P. L. Tam ◽  
Naihe Jing

Abstract Establishment of progenitor cell populations and lineage diversity during embryogenesis and the differentiation of pluripotent stem cells is a fascinating and intricate biological process. Conceptually, an understanding of this developmental process provides a framework to integrate stem-cell pluripotency, cell competence and differentiating potential with the activity of extrinsic and intrinsic molecular determinants. The recent advent of enabling technologies of high-resolution transcriptome analysis at the cellular, population and spatial levels proffers the capability of gaining deeper insights into the attributes of the gene regulatory network and molecular signaling in lineage specification and differentiation. In this review, we provide a snapshot of the emerging enabling genomic technologies that contribute to the study of development and stem-cell biology.


2020 ◽  
Author(s):  
Anna Badner ◽  
Emily K. Reinhardt ◽  
Theodore V. Nguyen ◽  
Nicole Midani ◽  
Andrew T. Marshall ◽  
...  

AbstractHuman neural stem cells (hNSCs) have potential as a cell therapy following traumatic brain injury (TBI). While various studies have demonstrated the efficacy of NSCs from on-going culture, there is a significant gap in our understanding of freshly thawed cells from cryobanked stocks – a more clinically-relevant source. To address these shortfalls, the therapeutic potential of our previously validated Shef-6.0 human embryonic stem cell (hESC)-derived hNSC line was tested following long-term cryostorage and thawing prior to transplant. Immunodeficient athymic nude rats received a moderate unilateral controlled cortical impact (CCI) injury. At 4-weeks post-injury, 6×105 freshly thawed hNSCs were transplanted into six injection sites (2 ipsi- and 4 contra-lateral) with 53.4% of cells surviving three months post-transplant. Interestingly, most hNSCs were engrafted in the meninges and the lining of lateral ventricles, associated with high CXCR4 expression and a chemotactic response to SDF1alpha (CXCL12). While some expressed markers of neuron, astrocyte, and oligodendrocyte lineages, the majority remained progenitors, identified through doublecortin expression (78.1%). Importantly, transplantation resulted in improved spatial learning and memory in Morris water maze navigation and reduced risk-taking behavior in an elevated plus maze. Investigating potential mechanisms of action, we identified an increase in ipsilateral host hippocampus cornu ammonis (CA) neuron survival, contralateral dentate gyrus (DG) volume and DG neural progenitor morphology as well as a reduction in neuroinflammation. Together, these findings validate the potential of hNSCs to restore function after TBI and demonstrate that long-term bio-banking of cells and thawing aliquots prior to use may be suitable for clinical deployment.Significance StatementThere is no cure for chronic traumatic brain injury (TBI). While human neural stem cells (hNSCs) offer a potential treatment, no one has demonstrated efficacy of thawed hNSCs from long-term cryobanked stocks. Frozen aliquots are critical for multisite clinical trials, as this omission impacted the use of MSCs for graft versus host disease. This is the first study to demonstrate the efficacy of thawed hNSCs, while also providing support for novel mechanisms of action – linking meningeal and ventricular engraftment to reduced neuroinflammation and improved hippocampal neurogenesis. Importantly, these changes also led to clinically relevant effects on spatial learning/memory and risk-taking behavior. Together, this new understanding of hNSCs lays a foundation for future work and improved opportunities for patient care.


2018 ◽  
Vol 115 (19) ◽  
pp. E4463-E4472 ◽  
Author(s):  
Geoffrey Lee ◽  
Ana Isabel Espirito Santo ◽  
Stefan Zwingenberger ◽  
Lawrence Cai ◽  
Thomas Vogl ◽  
...  

A major discovery of recent decades has been the existence of stem cells and their potential to repair many, if not most, tissues. With the aging population, many attempts have been made to use exogenous stem cells to promote tissue repair, so far with limited success. An alternative approach, which may be more effective and far less costly, is to promote tissue regeneration by targeting endogenous stem cells. However, ways of enhancing endogenous stem cell function remain poorly defined. Injury leads to the release of danger signals which are known to modulate the immune response, but their role in stem cell-mediated repair in vivo remains to be clarified. Here we show that high mobility group box 1 (HMGB1) is released following fracture in both humans and mice, forms a heterocomplex with CXCL12, and acts via CXCR4 to accelerate skeletal, hematopoietic, and muscle regeneration in vivo. Pretreatment with HMGB1 2 wk before injury also accelerated tissue regeneration, indicating an acquired proregenerative signature. HMGB1 led to sustained increase in cell cycling in vivo, and using Hmgb1−/− mice we identified the underlying mechanism as the transition of multiple quiescent stem cells from G0 to GAlert. HMGB1 also transitions human stem and progenitor cells to GAlert. Therefore, exogenous HMGB1 may benefit patients in many clinical scenarios, including trauma, chemotherapy, and elective surgery.


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