Contemporary nano-architectured drugs and leads for ανβ3 integrin-based chemotherapy: Rationale and retrospect

The integrins belong to the cell-surface polypeptide family and are the mediating partners among the cells, and extracellular matrix (ECM). They are also involved in the biological processes of cell migration, wound healing, blood clotting, immunological response generation, tissue morphogenesis, leucocyte reticulations, and angiogenesis and are therefore very relevant in stem cell technology and are useful as biomarkers, diagnostic probes, and drug-target ligands. The ανβ3 (alpha-nu-beta3) integrin antagonists are an excellent target example for designing and developing newer drug candidates, drug leads and templates for various diseases, and physiological malfunctioning, including cancers. The current review examines the ανβ3 integrin structural features involved in the drug design and its antagonistic ligands and highlights the development of anti-ανβ3 integrin-antagonists as nano-architectural design-based nanomedicine, especially for cancer chemotherapy. The perspectival review discusses the ανβ3 integrin structure, mode of action, involved pathways, and the concepts utilized in nanomedicine design, and ligands related to integrins. It also covers the latest thyrointegrin approaches toward the development of anti-angiogenesis agents and entails the anti-angiogenesis approach to cancer growth inhibition through targeting by the anti-integrin ligands and related chemical entities. The current perspective on the nano-architectural design approach for the known anti-integrin compounds is also outlined.

Creative regulatory practices to develop stem-cell technology: the way forward for Malaysia

Malaysia aspires to develop regenerative medicine through stem-cell technology. It needs a regulatory system that could facilitate development and prevent unethical practices. A comparative legal analysis on the regulation of stem-cell technology, with a focus on stem-cell research in Malaysia and selected Commonwealth countries that are experienced in regulating this complex technology, demonstrates that the selected Commonwealth countries have adopted a hybrid of different regulatory mechanisms. This paper argues that Malaysia should consider adopting a similar approach to equip relevant authorities with different regulatory mechanisms that are able to promote innovation in stem-cell research activities and cultivate a successful and profitable regenerative medicine industry in the future. Such a strategic action can produce an optimal regulatory outcome and help Malaysia to realize its aspiration.

Safety and Efficacy of Stem Cell Therapeutics in Wound Healing: A Rapid Review of Available Evidence

Background: Skin and wound injuries are important health problems with great mortality rates. While there are different alternative therapies, there is no agreement on the best therapy for burn wounds and wound complications. Stem cell therapy has an optimistic prospect in many preclinical studies of burn wounds and diabetic wounds. Objectives: In this study, we performed a rapid review to evaluate the efficacy and safety of stem cell therapy in wound treatment. Methods: This rapid review of the evidence aimed to evaluate the potential effects of stem cells on wound healing to create a policy guide for policymakers in the health care system. We searched such databases as PubMed and Scopus on March 13, 2021 using keywords, including “stem cells and wound healing”, “safety”, and “efficacy”. The references of retrieved studies were also checked to ensure the capture of the literature. Studies evaluating the safety and efficacy of stem cells on wound healing published in Persian and English were included. Generally, we used the PICO (population, intervention, control, and outcomes) model for search strategy. Results: Out of a total of 92 retrieved papers, 22 studies were eligible for inclusion. The overall review showed that stem cell therapy improved wounds. Also, studies showed that using stem cell technology in a non-invasive way could be a good alternative. However, the limitations of this technology consisted of the need to improve cell delivery methods, cell sustainability, heterogeneity in the research of mesenchymal stem cells, and wound substrate. Further studies are needed to determine its safety and efficacy. Conclusions: Although the evidence on the safety and efficacy of using stem cells for wound healing was limited, studies showed that stem cell technology is a good alternative to traditional therapies. Future clinical studies should consider the differences in the studies to achieve maximum effectiveness.

Cell Transplantation Therapies to Reverse Type 1 Diabetes: A review

Stem cell technology is demonstrating promising advancements in cure of diseases due its differentiation ability. Type 1 diabetes is mainly caused by autoimmune ? cells destruction. In this review, we focus on treatment procedures of Type 1 Diabetes (T1D) with numerous stem cells (SCs) i.e hPSCs, MSCs, hESCs, BMSCs, AFSCs, HSCs and islet cells (that are not stem cells but they are approved worldwide and are being successfully used to permanently reverse T1D). A brief overview of this disease along with the advancements in treatment of T1D with stem cells is discussed. Biomaterial encapsulation to avoid immune rejection and improved immunomodulation and immune tolerance via drugs /bioengineering techniques makes the outcomes of SC therapies more efficient and productive, hence, proving to be another future milestone of completely reversing type 1 diabetes especially in those patients who got clinically diagnosed at an early stage and then received prompt treatment of either restoration of already available ? cells functionality or transplantation of purified and functional SCs differentiated insulin producing cells to normalize the glycemic control and homeostasis. Keywords: Type 1 Diabetes, ?-cells, Stem cells, Biomaterial

Challenges and opportunities for modeling monogenic and complex disorders of the human retina via induced pluripotent stem cell technology

The human retina is a highly structured and complex neurosensory tissue central to perceiving and processing visual signals. In a healthy individual, the close interplay between the neuronal retina, the adjacent retinal pigment epithelium and the underlying blood supply, the choriocapillaris, is critical for maintaining eyesight over a lifetime. An impairment of this delicate and metabolically highly active system, caused by genetic alteration, environmental impact or both, results in a multitude of pathological phenotypes of the retina. Understanding and treating these disease processes are motivated by a marked medical need in young as well as in older patients. While naturally occurring or gene-manipulated animal models have been used successfully in ophthalmological research for many years, recent advances in induced pluripotent stem cell technology have opened up new avenues to generate patient-derived retinal model systems. Here, we explore to what extent these cellular models can be useful to mirror human pathologies in vitro ultimately allowing to analyze disease mechanisms and testing treatment options in the cell type of interest on an individual patient-specific genetic background.

Stem Cell Technology in Regenerative Medicines and Cancer Treatment: Towards Revolution in Clinical Success

Stem cells are undifferentiated, immature, and unspecialized cells having huge potential for differentiation and proliferation into the specialized functionalized cells. More recently, CSC has been described in breast cancer and brain tumors where they make up as few as 1% of the cells in a tumor. The features of cancer stem cells are just like normal stem cells but their replication rate many times faster than normal cells. Regenerative medicines are based on stem cells, are potentially useful to regenerate damaged cells, tissues, organs and replace cancer cells with normal cells. Induced pluripotent stem cells are the most important candidates for regenerative medicines, tissue engineering, cell reprogramming, and 3D printing. Cancer Stem Cells (CSCs) have a tumorinitiating capacity and play crucial roles in tumor metastasis, relapse and chemo/ radioresistance. Because CSCs are resistant to chemotherapeutic drugs and cause recurrence of cancer and also have the ability to be regenerated; they can cause serious problems in the treatment of various cancers. Numerous biocompatible biomaterials, miRNAs, nanomaterial, artificial intelligence, and machine learning are uses to reprograms stem cells into regenerative medicines for the treatment of cancer. The present paper describes the applications and importance of stem cells in regenerative medicines, cancer stem cells targeting therapies, and the role of miRNAs in cancer stem cells targeting.

Modeling Cardiomyopathies in a Dish: State-of-the-Art and Novel Perspectives on hiPSC-Derived Cardiomyocytes Maturation

The stem cell technology and the induced pluripotent stem cells (iPSCs) production represent an excellent alternative tool to study cardiomyopathies, which overcome the limitations associated with primary cardiomyocytes (CMs) access and manipulation. CMs from human iPSCs (hiPSC–CMs) are genetically identical to patient primary cells of origin, with the main electrophysiological and mechanical features of CMs. The key issue to be solved is to achieve a degree of structural and functional maturity typical of adult CMs. In this perspective, we will focus on the main differences between fetal-like hiPSC-CMs and adult CMs. A viewpoint is given on the different approaches used to improve hiPSC-CMs maturity, spanning from long-term culture to complex engineered heart tissue. Further, we outline limitations and future developments needed in cardiomyopathy disease modeling.