Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Immunology, Endocrine and Metabolic Agents) - Volume 15, Issue 2, 2015

Rise in the frequency of age-related diseases (neurodegenerative and cardiovascular diseases, osteoporosis, etc.) has great socio-economic implications. Great pathogenetic significance of age changes in functioning of the immune and neuroendocrine systems and their relationship with dysfunction of the central organs (thymus and pineal gland) has been established. On the contrary, melatonin and thymic hormones not only inhibit age changes in functioning of the above systems and diminish the incidence of age-related diseases but also improve their clinical results. Inhibiting effects of thymus and pineal gland factors on the development of age-related diseases can also be explained by their action on biological properties (proliferating and differential potential) of proper stem cells of different types in the organism organs. Noteworthy, the effect of melatonin on certain types of stem cells is realized not only directly but also indirectly via alteration of thymic endocrine function and functioning of endocrine glands. Thus, the pineal gland can provide adaptive (rhythmical) changes of the proliferative and differential potential of proper stem cells. Transplantation of different types of stem cells is used as stem therapy during already developed disorders. Nevertheless, at these diseases, the age-related dysfunction of the thymus and pineal gland is enhanced along with the changes in body organs interrelations. Therefore, therapeutic effects of stem cells transplantation can show themselves or be enhanced against the background of renewal of rhythmicity of pineal-thymus interactions. Maintenance of immune-endocrine interactions involving thymus and pineal gland plays role in the stem cell therapy of age-related diseases.

Adult stem cells and their potential in clinical applications have been intensively investigated in the past decade. Mesenchymal stem cells (MSCs) represent adult tissue stem cells: Bone marrow, cord blood, umbilical cord, and recently, adipose tissues are used as major sources of MSCs. Because of less ethical concerns as well as easier cell culture to propagate, MSC-based therapies sound promising for clinical settings. Several groups have demonstrated MSCs’ potential to differentiate into neurogenic lineage. This capability prompts us to apply MSCs for regeneration or replacement of damages neuronal cells in the brain. However, their application may be severely limited by the physical barrier-blood-brain barrier-under certain situations. In addition to neuronal differentiation capacity of MSCs, some of soluble factors released by MSCs may be beneficial to mitigate neuronal diseases. In this short review, I would like to discuss how we could utilize MSCs for the treatment of two major age-related neuronal diseases, Alzheimer’s and Parkinson’s diseases.

Cancer is one the most common life-threatening diseases. Cancer cases worldwide are forecast to rise by 75% in the future. Although cancer therapies have been improved, many tumors remain unresponsive to conventional treatments, such as radiation and chemotherapy. Therefore, novel strategies in treating and managing the disease are urgently needed. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have recently been shown to possess anti-cancer activities as well as tumor-homing ability. These cells are able to migrate to sites of neoplastic growth in vivo and their secretory products display tumoricidal activity both in vitro and in vivo models of human cancer. Recent reports also suggest that the anti-cancer potential of WJ-MSCs can also be enhanced through genetic engineering. This review will summarize the current understanding on the interactions between WJ-MSCs and tumor cells, as well as the potential use of both un-engineered and engineered WJ-MSCs as an anti-cancer agent.

The discovery of adult stem cells represents a milestone for the last decade research, due to their potential use in the field of regenerative therapy. Adult stem cells exist in all human tissues because they support tissue homeostasis and help in renewal and healing processes. Similar to human Embryonic Stem Cells (hESCs), adult stem cells are able to self-renew and differentiate into specialized cells of different embryonic germ layers. Their high plasticity makes them a good candidate in regenerative therapy. Adult stem cells may be suitable to treat common age-related diseases as neurodegenerative syndromes, heart failure, diabetes, cancer such as autoimmune diseases. The high plasticity of adult stem cells allows them to integrate into the host tissue after transplantation. As a consequence, a new microenvironment establishes, which promotes neo-angiogenesis and healing processes. However, recent findings showed that cancer cells are able to modify the microenvironment and dictate a tumorigenic role in support of cancer onset and progression. Altogether these findings raise some concerns about the safety of adult stem cells for treatment of cancer patients. In this review, we discuss past findings and future challenges about the development of stem cell therapies for treatment of cancer patients and examine the extent to which it would be affected by cancer microenvironment.

It is well established that aging is a significant risk factor for homeostatic imbalance, decline in vascular regenerative capacity and development of vascular disease with progressive organ dysfunction. Over the past decade therapeutic developments have improved the prognosis for those with vascular disease, mortality rates have nevertheless remained actually unchanged. Clearly, there is a need for alternative strategies for the treatment of vascular disease. Adipose tissue and bone marrow have been shown to contain adult mesenchymal stem cells that have therapeutic applications in regenerative medicine. In vivo experiments suggest that these cells are capable of replacing ischemic damaged tissues. The potential use of cell-based therapeutic angiogenesis has been proposed as an alternative treatment solutions for age-related vascular disease. This review outlines the current knowledge about adipose tissue and bone marrow as a sources of stem and progenitor cells, these cells contribution to ischemic damaged tissues regenerative processes and factors that may affect their decreased function in aging individuals. Moreover, it was described the cell-based therapeutic strategies that are currently being tested in clinical trials as well as clinical outcomes demonstrated after cell transplantation and emphasize possible mechanisms counteracting pathophysiological events of ischemia.

Background: Proteoglycan is one of the components of the extracellular matrix with various biological activities and has been used as the functional foods to improve knee joint health or skin condition. Objective: To examine the effect of ingestion of salmon (Oncorhynchus keta, Salmonidae) nasal cartilage-derived proteoglycan (sPG) on skin condition, we performed a randomized, double-blind, controlled study in healthy adult volunteers. Methods: Recruited subjects (n=156) were men and women, ages 21-62 years. From this population, we selected 19 subjects based on the exclusion criteria of the guidelines for evaluation of cosmetic functions of Japanese Cosmetic Science Society. Subjects were randomly divided into an sPG group (n=10; mean age, 39.1 years) and a placebo group (n=9; mean age, 39.6 years). The characteristics of the sPG used in this study were assessed by HPLC and electrophoresis analysis. Results: The safety was confirmed by the monitoring of all volunteer subjects for the development of adverse reactions. We found no negative information on the safety of proteoglycan ingestion and no evidence for an interaction between proteoglycan and other functional foods/medicine in several different databases. Viscoelasticity and recovery after deformation as the skin elasticity increased significantly in the sPG group compared to the placebo group (p<0.05). Skin looseness significantly decreased in the sPG group (p<0.05). Moreover, the number of wrinkles, conspicuous or darkened facial pores, and blotches significantly decreased in the sPG group (p<0.05). Measurements of skin conductance showed that sPG improved skin moisture and micrographs of facial corneocytes showed that sPG improved rough skin. Conclusion: Our results suggest the potential of sPG as a food ingredient to improve human skin condition, including skin elasticity, wrinkles, facial pores, blotches, moisture, and smoothness.

Azidothymidine (AZT) was the first breakthrough drug developed for the treatment of acquired immunodeficiency syndrome (AIDS). It took AZT only 25 months from the first successful laboratory activity against human immunodeficiency virus (HIV) to its approval by the FDA. Similar interesting facts and disputes have persistently been associated with AZT starting from its very first synthesis to the development and approval as drug. This review briefly collates the exciting history of AZT and, as the different stages involved in the discovery and the development of this drug molecule gets recapitulated here, could well serve as a mnemonic for the area of drug discovery and development in general.