Dietary phytochemical approaches to stem cell regulation

Hair follicles undergo lifelong growth and hair cycle is a well-controlled process involving stem cell proliferation and quiescence. Hair bulge is a well-characterized niche for adult stem cells. This segment of the outer root sheath contains a number of different types of stem cells, including epithelial stem cells, melanocyte stem cells and neural crest like stem cells. Hair follicles represent an accessible and rich source for different types of human stem cells. We and others have isolated neural crest stem cells (NCSCs) from human fetal and adult hair follicles. These human stem cells are label-retaining cells and are capable of self-renewal through asymmetric cell division in vitro. They express immature neural crest cell markers but not differentiation markers. Our expression profiling study showed that they share a similar gene expression pattern with murine skin immature neural crest cells. They exhibit clonal multipotency that can give rise to myogenic, melanocytic, and neuronal cell lineages after in vitro clonal single cell culture. Differentiated cells not only acquire lineage-specific markers but also demonstrate appropriate functions in ex vivo conditions. In addition, these NCSCs show differentiation potential toward mesenchymal lineages. Differentiated neuronal cells can persist in mouse brain and retain neuronal differentiation markers. It has been shown that hair follicle derived NCSCs can help nerve regrowth, and they improve motor function in mice transplanted with these stem cells following transecting spinal cord injury. Furthermore, peripheral nerves have been repaired with stem cell grafts, and implantation of skin-derived precursor cells adjacent to crushed sciatic nerves has resulted in remyelination. Therefore, the hair follicle/skin derived NCSCs have already shown promising results for regenerative therapy in preclinical models. Somatic cell reprogramming to induced pluripotent stem (iPS) cells has shown enormous potential for regenerative medicine. However, there are still many issues with iPS cells, particularly the long-term effect of oncogene/virus integration and potential tumorigenicity of pluripotent stem cells have not been adequately addressed. There are still many hurdles to be overcome before iPS cells can be used for regenerative medicine. Whereas the adult stem cells are known to be safe and they have been used clinically for many years, such as bone marrow transplant. Many patients have already benefited from the treatment. Autologous adult stem cells are still preferred cells for transplantation. Therefore, the readily accessible and expandable adult stem cells in human skin/hair follicles are a valuable source for regenerative medicine.

Hair follicles undergo lifelong growth and hair cycle is a well-controlled process involving stem cell proliferation and quiescence. Hair bulge is a well-characterized niche for adult stem cells1. This segment of the outer root sheath contains a number of different types of stem cells, including epithelial stem cells2, melanocyte stem cells3 and neural crest like stem cells4-7. Hair follicles represent an accessible and rich source for different types of human stem cells. We and others have isolated neural crest stem cells (NCSCs) from human fetal and adult hair follicles4,5. These human stem cells are label-retaining cells and are capable of self-renewal through asymmetric cell division in vitro. They express immature neural crest cell markers but not differentiation markers. Our expression profiling study showed that they share a similar gene expression pattern with murine skin immature neural crest cells. They exhibit clonal multipotency that can give rise to myogenic, melanocytic, and neuronal cell lineages after in vitro clonal single cell culture. Differentiated cells not only acquire lineage-specific markers but also demonstrate appropriate functions in ex vivo conditions. In addition, these NCSCs show differentiation potential toward mesenchymal lineages. Differentiated neuronal cells can persist in mouse brain and retain neuronal differentiation markers. It has been shown that hair follicle derived NCSCs can help nerve regrowth, and they improve motor function in mice transplanted with these stem cells following transecting spinal cord injury8. Furthermore, peripheral nerves have been repaired with stem cell grafts9, and implantation of skin-derived precursor cells adjacent to crushed sciatic nerves has resulted in remyelination10. Therefore, the hair follicle/skin derived NCSCs have already shown promising results for regenerative therapy in preclinical models. Somatic cell reprogramming to induced pluripotent stem (iPS) cells has shown enormous potential for regenerative medicine. However, there are still many issues with iPS cells, particularly the long term effect of oncogene/virus integration and potential tumorigenicity of pluripotent stem cells have not been adequately addressed. There are still many hurdles to be overcome before iPS cells can be used for regenerative medicine. Whereas the adult stem cells are known to be safe and they have been used clinically for many years, such as bone marrow transplant. Many patients have already benefited from the treatment. Autologous adult stem cells are still preferred cells for transplantation. Therefore, the readily accessible and expandable adult stem cells in human skin/hair follicles are a valuable source for regenerative medicine.

Stem cells are promising candidates for cell-based therapies in diverse conditions including regenerating damaged tissues, treating inflammation in virtue of sepsis, acute renal failure, and cardiovascular disease. Advancement of these therapies relies on the ability to guide stem cells to migrate directly and differentiate towards specific cell phenotypes. During the past decade, many researchers have demonstrated that exogenous applied forces could significantly affect the migration and lineage differentiation of stem cells. Besides, recent advances have highlighted the critical role of internal forces due to cell-matrix interaction in the function of stem cells. Stem cells can generate contractile forces to sense the mechanical properties of cell-generated force microenvironment, and thereby perceive mechanical information that directs broad aspects of stem cell functions, including migration and lineage commitment. In the review, we recount the cell-generated force microenvironment of stem cells and discuss the interactions between cell-generated forces with migration and differentiation of stem cells. We also summarize key experimental evidence of a tight linkage between migration and lineage differentiation of stem cells and pose important unanswered questions in this field.

To review the recent research progress of different types of stem cells in the treatment of ischemic stroke. By searching the PubMed database, a systematic review had been carried out for the results of applying different types of stem cells in the treatment of ischemic stroke between 2000 and 2020. Stem cells can be transplanted via intracranial, intravascular, cerebrospinal fluid, and intranasal route in the treatment of ischemic stroke. Paracrine and cell replacement are the two major mechanisms of the therapy. The researches have mainly focused on utilization of neural stem cells, embryonic stem cells, and mesenchymal stem cells. Each has its own advantages and disadvantages in terms of capability of migration, survival rate, and safety. Certain stem cell therapies have completed phase one clinical trial. Stem cells transplantation is feasible and has a great potential for the treatment of ischemic stroke, albeit that certain obstacles, including the selection of stem cells, transplantation strategy, migration ability, survival rate, still wait to be solved.

Spinal cord injury (SCI) has remained a challenging area for scientists and clinicians due to the adverse and complex nature of its pathobiology. To date, clinical therapies for debilitating SCI are largely ineffective. However, emerging research evidence suggests that repair of SCI can be promoted by stem cell-based therapies in regenerative medicine. Over the past decade, therapeutic potential of different types of stem cells for the treatment of SCI have been investigated in preclinical models. These studies have revealed multiple beneficial roles by which stem cells can improve the outcomes of SCI. This chapter will summarize the recent advances in the application of stem cells in regenerative medicine for the repair of SCI.

The idea of being able to replace, restore, or regenerate damaged or diseased tissues and organs in order to establish normal function in the human body has never been so prominent and possible than with the development of the field of regenerative medicine. Using material from the body or activating the body’s own repair mechanisms to prepare and grow or heal irreparable tissues or organs is now a real possibility, as demonstrated by research and clinical studies published over the last 10 years. Born from the collaboration of several biomedical disciplines and clinical approaches, regenerative medicine promises the real possibility of not only replacing pharmaceutical solutions to disease but also paves the road to a more autologous and holistic approach in clinical treatment of disease and disease control. Historically, the foundation of regenerative medicine was cemented with the successful transplantation of corneas, soft tissue, and bone in the early twentieth century. The first kidney transplantation in 1954 was followed by pancreas, liver, and heart transplants in the 1960s and success continued in the 1980s with heart– lung and living donor liver and lung transplants. Progressively, an increase in demand for tissues and organs and subsequent decrease in organ availability has left a need for new technology to meet the demand for suitable organs and organ donors as well as leading to an increase in the disgraceful enterprise of black market organs. Currently, tissueengineered skin used for burn survivors and diabetic ulcers, products derived from tissue engineering to induce bone growth and regeneration, as well as the autologous reintroduction of ex-vivo engineered bladder are a reality, once again establishing a firm foothold for the development of further and more advanced applications for regenerative medicine. The discovery of stem cells by the Russian histologist Alexander Maksimov in 1908, as part of his theory of hematopoiesis followed by Joseph Altman and Gopal Das in the 1960s presenting evidence of constant stem cell activity in the brain and the demonstration of self-renewing cells found in the bone marrow of mice by James E. Till and Ernest A. McCulloch in 1963, established stem cell research and the development of stem cell therapy as a new and very promising and exciting discipline for regenerative medicine. Embryonic and adult stem cells are available from a variety of sources and hold variable differentiation potential, not to mention the myriad potential therapeutic applications, albeit associated with some ethical and political concerns. Mammalian stem cells can be sourced from either the embryo or the adult organism. Embryonic stem cells originate from the inner cell mass of blastocysts, whereas adult stem and progenitor cells can be found in various tissues repairing or replenishing adult tissue. Of specific interest and application in regenerative medicine are autologous adult stem cells accessible from bone marrow, adipose tissue, or blood. Contemporary stem cell therapy includes bone marrow transplants for the treatment of leukemia, whereas extensive current research is undertaken for the implementation of stem cell therapy for the treatment of cancer, spinal cord injuries, and Parkinson’s disease, as well as multiple sclerosis and muscle conditions including heart disease. The use of vascular grafts for heart bypass surgery and cardiovascular disease treatment have been researched extensively and are at the pre-clinical trial stage. Advances in therapeutic applications do not come without much debate and controversy surrounding risks associated with it. The risk that transplanted stem cells could form tumors and metastasize uncontrollably is but one of the concerns of stem cell therapy. Inducing forced expression of specific genes in order to derive pluripotent stem cells from non-pluripotent cells generate the so-called induced pluripotent stem cell (iPSC). However, significant risk is associated with reprogramming of adult cells to obtain iPSCs. Potentially, this risk could limit their use in patients. The use of viruses to genomically alter the cells may lead to the expression of cancer-causing oncogenes. Low-level laser therapy (LLLT) has been scientifically proven as a beneficial therapeutic modality for numerous diseases and diseased conditions. Using very specific laser and light-emitting diode irradiation parameters, specific cellular activities can be induced, namely, cellular proliferation and viability while stimulating mitochondrial activity, thereby increasing adenosine triphosphate (ATP) production, synthesis of DNA and RNA, and activating cellsignaling cascades including the production of reactive oxygen species (ROS), nitric oxide (NO) release, activating cytochrome c oxidase, and modifying intracellular organelle membrane activity, calcium flux, and expression of stress proteins. The molecular mechanism underlying these cellular activities is less well understood, and several research groups are conducting intensive research studies in an effort to elucidate the relation between these biological

Stem cells are located in a well-structured and specialized microenvironment called the niche. The niche provides signaling molecules to control the survival, self-renewal, and differentiation of stem cells. As tissues generally contain different types of stem cells, it is important to understand how these stem cells are coordinately regulated by various signaling pathways. The Drosophila testis niche serves as an excellent model for studying such processes, because it harbors 2 types of stem cells, germline stem cells and somatic cyst stem cells. In this review, we summarize the roles of key signaling pathways in stem cell maintenance and differentiation in the Drosophila testis.

<h3>Introduction and history</h3> While regenerative medicine may seem like a novel intervention in the chronic pain armamentarium, its evolution and in a sense its definition has been intricately related to...

Regenerative Medicine and Rehabilitation Therapy in the Canine

Stem cells are undifferentiated cells that are capable of renewal and repair of tissue due to their capacity for division and differentiation. The purpose of this review is to describe recent advances in the use of stem cell (SC) therapy for male erectile dysfunction (ED). We performed a MEDLINE database search of all relevant articles regarding the use of SCs for ED. We present a concise summary of the scientific principles behind the usage of SC for ED. We discuss the different types of SCs, delivery methods, current pre-clinical literature, and published clinical trials. Four clinical trials employing SC for ED have been published. These articles are summarized in this review. All four report improvements in ED after SC therapy. SC therapy remains under investigation for the treatment of ED. It is reassuring that clinical trials thus far have reported positive effects on erectile function and few adverse events. Safety and methodical concerns about SC acquisition, preparation and delivery remain and require continued investigation prior to wide-spread application of these methods.

Regenerating Hearing: Researchers Begin First-Ever Study of Stem Cells to Treat Hearing Loss

Stem cell therapies may be valuable in treatment of inflammatory bowel disease (IBD). Here we focus on two very different types of stem cells – hematopoietic stem cells and mesenchymal stem cells. Myeloablation and hematopoietic stem cell transplantation alter host immune response by reconstituting the recipient’s blood cell lines with donor cells. Autologous hematopoietic reconstitution may “reboot” mucosal immunity to a normal baseline state, but does not alter any underlying genetic predisposition to IBD. In contrast, allogeneic hematopoietic transplantation reconstitutes all blood lineages from a tissue-matched donor who presumably does not have a genetic predisposition to IBD. Compared with autologous hematopoietic transplantation, allogeneic hematopoietic transplantation carries a much greater risk of complications, including graft-versus-host disease. Mesenchymal stem cells can give rise to cartilage, bone and fat in vitro, but do not reconstitute hematopoiesis after transplantation. Systemically infused mesenchymal stem cells appear to favorably downregulate host immune responses through poorly understood mechanisms. In addition, mesenchymal stem cells may be applied topically to help close fistulas associated with Crohn’s disease. For all of these stem cell therapy applications for IBD, only cases and small series have been reported. Larger clinical trials are planned or ongoing.

Nanoarchitectonics has emerged as a post-nanotechnology concept. As one of the applications of nanoarchitectonics, this review paper discusses the control of stem cell fate and function as an important issue. For hybrid nanoarchitectonics involving living cells, it is crucial to understand how biomaterials and their nanoarchitected structures regulate behaviours and fates of stem cells. In this review, biomaterials for the regulation of stem cell fate are firstly discussed. Besides multipotent differentiation, immunomodulation is an important biological function of mesenchymal stem cells (MSCs). MSCs can modulate immune cells to treat multiple immune- and inflammation-mediated diseases. The following sections summarize the recent advances of the regulation of the immunomodulatory functions of MSCs by biophysical signals. In the third part, we discussed how biomaterials direct the self-organization of pluripotent stem cells for organoid. Bioactive materials are constructed which mimic the biophysical cues of in vivo microenvironment such as elasticity, viscoelasticity, biodegradation, fluidity, topography, cell geometry, and etc. Stem cells interpret these biophysical cues by different cytoskeletal forces. The different cytoskeletal forces lead to substantial transcription and protein expression, which affect stem cell fate and function. Regulations of stem cells could not be utilized only for tissue repair and regenerative medicine but also potentially for production of advanced materials systems. Materials nanoarchitectonics with integration of stem cells and related biological substances would have high impacts in science and technology of advanced materials.

Chapter 6 - Human pluripotent nontumorigenic multilineage differentiating stress enduring (Muse) cells isolated from adipose tissue: A new paradigm in regenerative medicine and cell therapy

Novel Evidence for the Presence of Potent, Paracrine, Pro-Angiopoietic Effects of Purified Human Umbilical Cord Blood-Derived CD133+ Cells - Implications for Adult Stem Cell Therapies in Regenerative Medicine