Stimulate Cell Regeneration Research Articles

Hyperbaric Oxygen and Regenerative Medicine: Non-Traditional Uses to Help Reduce Inflammation, Stimulate Cell Regeneration and Improve Healing

Hyperbaric oxygen therapy (HBOT) is US FDA approved for a short list of 14 severe, life-threatening conditions. These FDA approved conditions range from osteomyelitis, osteonecrosis and gangrene to non-healing wounds, diabetic neuropathy, crush injuries, radiation burns and more. When applied in acute and severe conditions, this therapy is noninvasive, safe, and effective in promoting patient recovery, improved healing times, and increased tissue regeneration. Alternatively, chronic inflammatory illnesses affect a larger population, cost our medical system billions of dollars every year, impair our quality of life, and reduce our ability to contribute to society. Some of these conditions include autoimmunity, neurodegenerative and musculoskeletal degenerative diseases, cardiovascular disease, cancer and many others. Common denominators for many of these illnesses include chronic inflammation, metabolic and mitochondrial dysfunction and immune dysregulation. The majority of studies for HBOT point to about 10 very specific mechanisms of action when used for the more conventionally treated conditions. There is mounting evidence that the mechanisms of action for these “on label” acute and severe cases are similar or even identical to those required for treating other chronic illnesses to improve their outcomes and recovery times. Hyperbaric oxygen can be delivered a number of ways, from mild pressure to high pressure and from 21% oxygen through 100% oxygen. Current research also shows that intermittent and relative hyperoxia-hypoxia is a strong stimulator of many cell signaling and epigenetic signaling cascades used for the promotion of and adaptation to improved cellular healing and regenerative responses. The research on these concepts is currently in its infancy but recent studies have shown that HBOT, through its influences on hypoxia-inducible factor 1α, reactive oxygen species signaling and sirtuin stimulation can help to promote hormonal balance, nervous system balance, improve mitochondrial performance, reduce inflammation and stimulate cell and tissue repair and regeneration for many different health concerns. Another study published in 2019 also showed us that using hyperbaric oxygen can also stimulate telomere growth and reduce cellular senescence, putting HBOT within the category of optimal modalities to be considered for a well-rounded antiaging and regenerative medicine approach to improved health and quality of life.

Short peptides stimulate cell regeneration in skin during aging

The search for new safe and efficient low-molecular weight substances stimulating skin regeneration is an important objective of geriatric cosmetology. The present study addressed the effects of the peptides LK and AEDG at concentrations of 0.05–2.00 ng/mL on the proliferation of organotypic tissue cultures of skin from young and old animals. The application of peptides enhanced fibroblast proliferation in skin cell cultures from young and old animals by 29–45%. The effect on aging skin was observed in a narrower concentration range; in addition, it was less pronounced than the effect on skin cell cultures obtained from young animals. These data reveal the potential of LK and AEDG as components of cosmetic products that restore the structure of aging skin.

484 BLADDER OVERDISTENSION STIMULATES UROTHELIAL PROLIFERATION WITHOUT APOPTOSIS

You have accessJournal of UrologyPediatrics: Neuropathic Bladder/Reconstruction1 Apr 2013484 BLADDER OVERDISTENSION STIMULATES UROTHELIAL PROLIFERATION WITHOUT APOPTOSIS Christina B Ching, Heidi A Stephany, Mariana M Cajaiba, Stacy T Tanaka, John C Thomas, John C Pope, Mark C Adams, John W Brock, and Douglass B Clayton Christina B ChingChristina B Ching Nashville, TN More articles by this author , Heidi A StephanyHeidi A Stephany Nashville, TN More articles by this author , Mariana M CajaibaMariana M Cajaiba Nashville, TN More articles by this author , Stacy T TanakaStacy T Tanaka Nashville, TN More articles by this author , John C ThomasJohn C Thomas Nashville, TN More articles by this author , John C PopeJohn C Pope Nashville, TN More articles by this author , Mark C AdamsMark C Adams Nashville, TN More articles by this author , John W BrockJohn W Brock Nashville, TN More articles by this author , and Douglass B ClaytonDouglass B Clayton Nashville, TN More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1876AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have previously shown that bladder overdistension causes hypoxic and ischemic bladder injury. Interested in restorative responses of the bladder, we hypothesized that bladder overdistension would stimulate cell regeneration. METHODS Female C57/Bl6 mice were ovariectomized at 6 weeks. Two experimental mice groups underwent bladder overdistension via catheterization and 0.9% saline infusion at 60cmH20 for 90 minutes under isoflurane general anesthesia. One group (acute distension group) was sacrificed immediately after a single distension (time=0), and at 3 hours (t=3), 6 hours (t=6), and 24 hours (t=24) after recovery. Another group (chronic distension group) underwent a single, daily distension for 5 consecutive days and were then sacrificed. Age-matched ovariectomized controls underwent general anesthesia only for these time points. Bladder tissue was harvested and stained for H&E. Immunohistochemistry was performed for caspase-3 (apoptotic indicator) and Ki-67 (proliferative indicator). In a separate chronic group, Bromodeoxyuridine (BRDU) (proliferative indicator) was injected intraperitoneally 2 hours before sacrifice. Urothelial proliferation was quantified by counting percentage positively staining cells at 400x power. RESULTS Specific histologic differences were observed in experimental groups versus controls. H&E in the acute group demonstrated immediate suburothelial hemorrhage (t=0) and increasing inflammation with time recovery (t=24). Transmural inflammation was observed in the chronic group. Ki-67 staining showed significant urothelial proliferation. At t=24, up to 92% of total urothelial cells were proliferating; in the chronic group, up to 60% were proliferating. In controls, t=0, and t=3, proliferation was seen in only up to 2%. FIGURE 1. Urothelial BRDU staining in the additional chronic group was increased as compared to controls (up to 15% vs. 1%). Caspase-3 staining showed no evidence of urothelial apoptosis in any group. CONCLUSIONS Bladder overdistension results in urothelial proliferation that begins 24 hours after injury. Evidence of apoptosis was not present. Characterizing the balance between urothelial cell death and proliferation can ultimately help understand the deleterious effects of bladder overdistension. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e199 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christina B Ching Nashville, TN More articles by this author Heidi A Stephany Nashville, TN More articles by this author Mariana M Cajaiba Nashville, TN More articles by this author Stacy T Tanaka Nashville, TN More articles by this author John C Thomas Nashville, TN More articles by this author John C Pope Nashville, TN More articles by this author Mark C Adams Nashville, TN More articles by this author John W Brock Nashville, TN More articles by this author Douglass B Clayton Nashville, TN More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Local In Vivo GSK3β Knockdown Promotes Pancreatic β Cell and Acinar Cell Regeneration in 90% Pancreatectomized Rat

Endocrine and exocrine insufficiencies are associated with serious diseases such as diabetes and pancreatitis, respectively. Pancreatic cells retain the capacity to regenerate in the context of cell deficiency. The remnant pancreas after pancreatectomy (Px) is a valuable target for testing the efficiency of pharmacological interventions to stimulate cell regeneration. Here, we tested the ability of GSK3β downregulation on the stimulation of β- and acinar cell regeneration after 90% Px in adult rats. We developed an in vivo approach based on local silencing of GSK3β, by delivering antisense morpholino-oligonucleotides within the remnant pancreas of 90% pancreatectomized rats, and evaluated its impact on the regenerative potential of pancreatic β and exocrine cells. β-Cell (BC) mass was evaluated by morphometry. Cell proliferation and apoptosis were assessed by 5'bromo 2'deoxyuridine (BrdU) incorporation method and TUNEL assay, respectively. The expression of Sox9, Neurogenin-3 (Ngn3), and PDX1 was evaluated by immunohistochemistry. We show that intrapancreatic GSK3β knockdown leads to increased BC mass (BCM) in 90% pancreatectomized rats by promoting both BC proliferation and differentiation. Moreover, downregulation of GSK3β significantly improves exocrine growth and prevents acinar cell apoptosis in vivo. Our study designates GSK3β as a viable drug target for therapeutic intervention on diseases of endocrine and exocrine pancreas associated with cell deficiency.

Cytokines and Myocardial Regeneration

The regenerative capacity of the myocardium and its blood vessels has now been well demonstrated. The cytokines granulocyte colony-stimulating factor, erythropoietin, and stem cell factor may play a role in helping to stimulate cell regeneration under normal physiologic conditions and in patients with myocardial injury. After an ischemic insult, cytokines are released into the peripheral circulation and signal for the mobilization of stem cells. In experimental cardiac injury models, the addition of cytokines has been shown to improve myocardial function with and without the concurrent use of stem cell therapy. Preliminary studies in humans using cytokine therapy alone for treating myocardial infarction have been disappointing. Future studies in patients with myocardial injury need to examine the use of various combinations of cytokines, with and without the addition of intravascular stem cell infusions or direct stem cell injections.

Hepatocyte growth factor in renal failure: Promise and reality

Can science discover some secrets of Greek mythology? In the case of Prometheus, we can now suppose that his amazing hepatic regeneration was caused by a peptide growth factor called hepatocyte growth factor (HGF). Increasing evidence indicates that HGF acts as a multifunctional cytokine on different cell types. This review addresses the molecular mechanisms that are responsible for the pleiotropic effects of HGF. HGF binds with high affinity to its specific tyrosine kinase receptor c-met, thereby stimulating not only cell proliferation and differentiation, but also cell migration and tumorigenesis. The three fundamental principles of medicine-prevention, diagnosis, and therapy-may be benefited by the rational use of HGF. In renal tubular cells, HGF induces mitogenic and morphogenetic responses. In animal models of toxic or ischemic acute renal failure, HGF acts in a renotropic and nephroprotective manner. HGF expression is rapidly up-regulated in the remnant kidney of nephrectomized rats, inducing compensatory growth. In a mouse model of chronic renal disease, HGF inhibits the progression of tubulointerstitial fibrosis and kidney dysfunction. Increased HGF mRNA transcripts were detected in mesenchymal and tubular epithelial cells of rejecting kidney. In transplanted patients, elevated HGF levels may indicate renal rejection. When HGF is considered as a therapeutic agent in human medicine, for example, to stimulate kidney regeneration after acute injury, strategies need to be developed to stimulate cell regeneration and differentiation without an induction of tumorigenesis.

Collagenase and gelatinase activities in bronchoalveolar lavage fluids during bleomycin-induced lung injury.

Basement membrane degradation can be indicative of tissue injury, but the process may also release matrix-bound cytokines to stimulate cell regeneration. To investigate this process, acute lung injury was induced in rats by intratracheal bleomycin and animals were killed from 3 days to 8 weeks later. The lungs were lavaged with saline to collect bronchoalveolar lavage (BAL) fluid and cell proliferation was assessed by pulse incorporation of tritiated thymidine. Bleomycin induced rapid inflammation with increased cell numbers and protein levels in BAL. Collagen degradation products were also increased in BAL fluid from 3 days to 4 weeks. Incubating samples of BAL fluid with radiolabelled collagens I and IV showed that high levels of activity, particularly for the degradation of type IV collagen, were present as early as 3 days post-bleomycin and persisted over the 8-week period. Zymograms demonstrated the highest level of gelatinase A (MMP-2) activity in BAL fluid in the first 2 weeks after bleomycin. Coincident with peak basement membrane degradative activity was the onset of a phase of epithelial cell proliferation, as measured by labelled nuclei in autoradiographs. The results show that enzymes capable of degrading the alveolar basement membrane are secreted early in the lung injury phase and that their presence in BAL fluid can be used as a measure of alveolar wall damage. It is possible that this enzyme action may release bound cytokines from the basement membrane, since maximal gelatinase activity correlates with alveolar epithelial cell proliferation.