The role of stem cells in anti-aging medicine

Aging is the result of two overlapping processes, “intrinsic” and “extrinsic.” Intrinsic structural changes occur as a consequence of physiologic aging and are genetically determined; extrinsic relates to exposure to harmful events and habits, like smoking, bad diet, alcohol consumption, lack of sleep, stress, sun exposure, environmental pollution, etc. Aging may be decelerated by improving bad habits or treating signs of aging with various esthetic methods, food supplements, and antioxidants. It is believed that we cannot stop aging entirely due to the intrinsic part, which leads to irreversible cell damage, as well as tissue and organ damage due to their limited ability to regenerate. Stem cells and their ability to exhibit telomerase activity, to self-renew, and to differentiate into all three embryonic tissues challenges aging as a process, which is not inevitable and can even possibly be reversed. Stem cells can promote regeneration of aged tissues and organs by replacing apoptotic and necrotic cells with healthy ones. In addition, they can have antiinflammatory and antiapoptotic properties by paracrine-secreting growth factors and cytokines on the site of administration. Autologous adipose-derived stem cells are the most promising because they can be easily harvested in huge numbers with minimally invasive liposuction and, as such, represent a powerful tool in anti-aging and regenerative medicine. In this contribution, the author discusses their properties and application in clinical practice.     

皮肤间充质干细胞在促进皮肤愈合中的作用

间充质干细胞(mesenchymal stem cells,MSCs)是当前干细胞研究的热点之一。目前,皮肤愈合正逐渐受到重视。现有的研究认为骨髓间充质干细胞(BM-MSCs)能从多个方面促进皮肤愈合,如促进表皮生长、促进真皮成纤维细胞的增生等。皮肤间充质干细胞(SMSCs)和BM-MSCs均为MSCs,具有很多的相似性,且SMSCs较BM-MSCs更容易得到。所以可从目前对BM-MSCs的研究预测到SMSCs在皮肤创伤愈合中的研究前景,且将来很可能会替代BM-MSCs。     

Exploring the role of stem cells in cutaneous wound healing

Abstract:  The skin offers a perfect model system for studying the wound healing cascade, which involves a finely tuned interplay between several cell types, pathways and processes. The dysregulation of these factors may lead to wound healing disorders resulting in chronic wounds, as well as abnormal scars such as hypertrophic and keloid scars. As the contribution of stem cells towards tissue regeneration and wound healing is increasingly appreciated, a rising number of stem cell therapies for cutaneous wounds are currently under development, encouraged by emerging preliminary findings in both animal models and human studies. However, we still lack an in-depth understanding of the underlying mechanisms through which stem cells contribute to cutaneous wound healing. The aim of this review is, therefore, to present a critical synthesis of our current understanding of the role of stem cells in normal cutaneous wound healing. In addition to summarizing wound healing principles and related key molecular and cellular players, we discuss the potential participation of different cutaneous stem cell populations in wound healing, and list corresponding stem cells markers. In summary, this review delineates current strategies, future applications, and limitations of stem cell-based or stem cell-targeted therapy in the management of acute and chronic skin wounds.     

Protective role of adipose-derived stem cells and their soluble factors in photoaging

As individuals age, the skin undergoes changes, such as irregular pigmentation, thinning and loss of elasticity, that are due to both genetic and environmental factors. These changes may worsen, progressing to precancerous and cancerous diseases. Various medical treatments and topical cosmeceuticals have been used to treat some symptoms of photoaging, however, the results have been less than satisfactory. Mesenchymal stem cells within the stromal-vascular fraction of subcutaneous adipose tissue, adipose-derived stem cells (ADSCs), display multi-lineage developmental plasticity and secrete various growth factors that control and manage the damaged neighboring cells. Recently, the production and secretion of growth factors has been reported as an essential function of ADSCs, and diverse regenerative effects of ADSCs have been demonstrated in the skin. For example, conditioned medium from ADSCs (ADSC-CM) stimulated both collagen synthesis and migration of dermal fibroblasts, which improved the wrinkling and accelerated wound healing in animal models. ADSC-CM also inhibited melanogenesis in B16 melanoma cells, and protected dermal fibroblasts from oxidative stress induced by chemicals and UVB irradiation. Therefore, ADSCs and soluble factors show promise for the treatment of photoaging, and this review introduces recent research developments of the ADSCs and ADSC-derived secretory factors regarding this issue.     

The advantages of hair follicle pluripotent stem cells over embryonic stem cells and induced pluripotent stem cells for regenerative medicine

Multipotent adult stem cells have many potential therapeutic applications. Our recent findings suggest that hair follicles are a promising source of easily accessible multipotent stem cells. Stem cells in the hair follicle area express the neural stem cell marker nestin, suggesting that hair-follicle stem cells and neural stem cells have common features. Nestin-expressing hair follicle stem cells can form neurons and other cell types, and thus adult hair follicle stem cells could have important therapeutic applications, particularly for neurologic diseases. Transplanted hair follicle stem cells promote the functional recovery of injured peripheral nerve and spinal cord. Recent findings suggest that direct transplantation of hair-follicle stem cells without culture can promote nerve repair, which makes them potentially clinically practical. Human hair follicle stem cells as well as mouse hair follicle stem cells promote nerve repair and can be applied to test the hypothesis that human hair follicle stem cells can provide a readily available source of neurologically therapeutic stem cells. The use of hair follicle stem cells for nerve regeneration overcomes critical problems of embryonic stem cells or induced pluripotent stem cells in that the hair follicle stem cells are multipotent, readily accessible, non-oncogenic, and are not associated with ethical issues.     

The role of T cells in psoriasis

Evidence for a key role of T cells in the pathogenesis of psoriasis has come from both experimental and clinical data. Initially, generalized immunosuppressants, intended for use in transplant settings, were found to improve clinical signs and symptoms of psoriasis. Their efficacy attracted attention to the activated T cells that are a major component of the inflammatory infiltrate of psoriatic lesions. Further research determined that T cells from patients with psoriasis could transmit disease in animal models. These findings laid the groundwork for characterizing the pathogenesis of psoriasis as immune mediated with skin-directed T cells playing a central role. Once these pathogenic T cells have entered the skin, they become activated and release cytokines and chemokines to attract other immune cells to perpetuate the inflammatory cascade. As the role of the T cell in psoriasis has evolved and understanding of immunopathology has increased, a multitude of biologic targets have been revealed. Newer strategies for the treatment of psoriasis have therefore focused on modifying T cells in this disease through direct elimination of activated T cells, inhibition of T-cell activation, or inhibition of cytokine secretion or activity. The mechanisms by which these new biologic agents act on psoriasis will affect their profile of efficacy and safety. Important selection criteria for optimal antipsoriatic therapies include long-term safety and tolerability, ability to produce long-lasting remissions, and convenient dosing regimens.     

The role of polymorphonuclear cells in psoriasis

Neutrophil cell function in psoriasis was studied through polymorphonuclear cell adherence to nylon wool, chemotaxis under agarose, and phagocytosis of Candida albicans. Differences in PMN adherence were not found between psoriatics and controls. The chemotactic response to zymosan activated serum (ZAS) did not differ between psoriatic and normal PMNs. The psoriatic serum exhibited chemoattracting properties equal to ZAS. Psoriatic serum was shown to be chemoattracting to psoriatic and normal PMNs whereas normal serum was only to psoriatic cells. Differences in recognition mechanisms between psoriatic and normal cells are proposed. Phagocytosis of Candida by psoriatic PMNS was earlier and more prolonged and candidacidal activity was earlier and definetely increased at given times compared to normal PMNs. A protective role of psoriatic PMNs in Munro's microabcesses against bacterial invasion is postulated.     

The role of dendritic cells in cutaneous immunity

This article reviews the role of dendritic cells in cutaneous immunity. Langerhans cells (LC) found in the epidermis are the best-characterized dendritic cell population. They have the ability to process antigen in the periphery, transport it to the draining lymph nodes (DLN) where they are able to cluster with, and activate, antigen-specific naive T cells. During migration LC undergo phenotypic and functional changes which enable them to perform this function. There are other less well-characterized dendritic cells including dendritic epidermal T cells, dermal dendrocytes and dermal ‘LC-like’ cells. Although there is no evidence that dendritic epidermal T cells (DETC) can present antigen or migrate to lymph nodes, they do influence the intensity of cutaneous immune responses to chemical haptens. Antigen-presenting cells (APC) in the dermis may provide alternative routes of antigen presentation which could be important in the regulation of skin immune responses. Therefore, dendritic cells are vital for the induction of immune responses to antigens encountered via the skin. LC are particularly important in primary immune responses due to their ability to activate naive T cells. The faster kinetics of secondary responses, and the ability of nonprofessional APC to induce effector function in previously activated cells, suggest that antigen presentation in the DLN may be less important in responses to previously encountered antigens. In these seondary responses, dendritic and nondendritic APC in the skin may directly induce effector functions from antigen-specific recirculating cells. Received: 24 April 1995     

树突状细胞在炎症性皮肤病中的作用

树突状细胞为皮肤内最重要的抗原提呈细胞，参与免疫反应全过程，其在各类炎症性皮肤病的发病中可能有重要意义。该文对炎症性皮肤病中的树突状细胞亚群，及其表面IgE受体结构和树突状细胞对T细胞亚群的分化迁移作用作一综述。     

The complex role of mast cells in fungal infections

In addition to their critical role in allergic disorders, mast cells (MCs) are well recognized for their protective effector functions during bacteria and parasite infections. This review describes recent advancements of our understanding of the complex role of MCs in fungal infections. Specifically, we outline key features of the contribution of MCs to infections with six fungal pathogens, namely Sporothrix, Paracoccidioides, Aspergillus, Malassezia, Candida and Dermatophytes. Evidence from studies of these pathogens suggests that MCs can function as positive regulators that detect and contain fungi at the site of infection. However, it appears that the inflammation induced by MCs following fungal infections may not always and only be beneficial to the host. MC responses during fungal infections may primarily benefit the pathogen by facilitating its spreading and contributing to a greater severity of fungal infections. This review also highlights key drivers of MCs activation and effector mechanisms that have been identified for the multidimensional function of MCs in fungal diseases and in allergic diseases combined with fungal infection.     

Melanocytes,melanocyte stem cells,and melanoma stem cells

Melanocyte stem cells differ greatly from melanoma stem cells; the former provide pigmented cells during normal tissue homeostasis and repair, and the latter play an active role in a lethal form of cancer. These 2 cell types share several features and can be studied by similar methods. Aspects held in common by both melanocyte stem cells and melanoma stem cells include their expression of shared biochemical markers, a system of similar molecular signals necessary for their maintenance, and a requirement for an ideal niche microenvironment for providing these factors. This review provides a perspective of both these cell types and discusses potential models of stem cell growth and propagation. Recent findings provide a strong foundation for the development of new therapeutics directed at isolating and manipulating melanocyte stem cells for tissue engineering or at targeting and eradicating melanoma specifically, while sparing nontumor cells.     

The possible role of mast cells in pigmented nevi

Summary Electron microscopic investigations revealed high numbers of mast cells in pigmented nevi particularly in the vicinity of blood vessels and unmyelinated nerve fibers. The elevated number of mast cells near the blood vessels is a well known phenomenon in various tissues. The very close contact between mast cells and smooth muscle cells of the vessels as well as the naked axons of unmyelinated nerve fibers may suggest a transport function of these cells from the blood circulation to the nervous system and/or vice versa. The significance of this transport function especially in the metabolism of nevus-tissue is discussed.

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Zusammenfassung Mit elektronenmikroskopischen Untersuchungen wurde an Naevuszell-Naevi eine häufige Zahl von Mastzellen besonders in der Nähe der Gefäße und marklosen Nervenfasern beobachtet. Die Vermehrung der Mastzellen im Gebiet der Blutgefäße der varianten Gewebe wurde als gut bekanntes Phenomen registriert. Auf Grund des sehr engen Kontaktes zwischen Mastzellen und glatten Muskelzellen der Blutgefäße sowie der nackten Axonen der marklosen Nervenfasern ist eine transportierende Funktion dieser Zellen aus der Blutzirkulation zum Nervensystem und vica versa vorauszusetzen. Die Bedeutung dieser transportierenden Funktion ist speziell im Stoffwechsel der Naevusgewebe besprochen.

     

固有淋巴样细胞2亚类与炎症性皮肤病

近年来新发现的一群表达CD45、具有淋巴细胞表型特征,但缺乏适应性免疫特有抗原特异性表面受体的免疫细胞,该群细胞被命名为固有淋巴样细胞(innate lymphoid cells,ILCs)。根据刺激因子、转录因子表达及产生效应因子的不同,ILCs可分为3类亚型,现有研究表明ILCs是淋巴器官发生、代谢的关键,也是组织稳态维持、修复,以及机体抵抗病毒、蠕虫感染的基础。此外ILCs也在皮肤中表达,并参与了皮肤创伤、特应性皮炎、接触性皮炎等皮肤炎症。     

干细胞在皮肤病中的应用

干细胞是存在于所有多细胞组织中,具有自我更新、增殖分化潜能的一种未分化细胞。干细胞的种类随研究的深入逐渐增多。干细胞治疗相关疾病的具体机制多数未明。目前在皮肤科领域,干细胞研究主要集中于皮肤损伤修复与组织工程学再生以及自身免疫相关性疾病、遗传性皮肤病、皮肤自然衰老与光老化、皮肤肿瘤等疾病治疗方面。干细胞应用的适应证随着研究的深入逐渐增加,特别在目前传统治疗方法棘手的自身免疫疾病、遗传性皮肤病、皮肤肿瘤等领域显示出优势。