Current Stem Cell Research & Therapy - Volume 15, Issue 3, 2020

Damaged or disabled tissue is life-threatening due to the lack of proper treatment. Many conventional transplantation methods like autograft, iso-graft and allograft are in existence for ages, but they are not sufficient to treat all types of tissue or organ damages. Stem cells, with their unique capabilities like self-renewal and differentiate into various cell types, can be a potential strategy for tissue regeneration. However, the challenges like reproducibility, uncontrolled propagation and differentiation, isolation of specific kinds of cell and tumorigenic nature made these stem cells away from clinical application. Today, various types of stem cells like embryonic, fetal or gestational tissue, mesenchymal and induced-pluripotent stem cells are under investigation for their clinical application. Tissue engineering helps in configuring the stem cells to develop into a desired viable tissue, to use them clinically as a substitute for the conventional method. The use of stem cell-derived Extracellular Vesicles (EVs) is being studied to replace the stem cells, which decreases the immunological complications associated with the direct administration of stem cells. Tissue engineering also investigates various biomaterials to use clinically, either to replace the bones or as a scaffold to support the growth of stemcells/ tissue. Depending upon the need, there are various biomaterials like bio-ceramics, natural and synthetic biodegradable polymers to support replacement or regeneration of tissue. Like the other fields of science, tissue engineering is also incorporating the nanotechnology to develop nano-scaffolds to provide and support the growth of stem cells with an environment mimicking the Extracellular matrix (ECM) of the desired tissue. Tissue engineering is also used in the modulation of the immune system by using patient-specific Mesenchymal Stem Cells (MSCs) and by modifying the physical features of scaffolds that may provoke the immune system. This review describes the use of various stem cells, biomaterials and the impact of nanotechnology in regenerative medicine.

Acute-on-Chronic Liver Failure (ACLF) is characterized by acute exacerbation of chronic hepatitis, organ failure, high mortality, and poor prognosis. At present, the clinical methods of treatment include comprehensive treatment with medicines, artificial liver system, and Orthotopic Liver Transplantation (OLT), and of these, OLT is considered the most effective treatment for ACLF. However, it is difficult for ACLF patients to benefit from OLT due to the shortage of liver donors, high cost, unpredictable postoperative complications, and long-term use of immunosuppressive drugs; therefore, it is important to explore a new treatment option. With the development of stem cell transplantation technology in recent years, several studies have shown that treatment of ACLF with Mesenchymal Stem Cells (MSCs) leads to higher survival rates, and has good tolerance and safety rates, thereby improving the liver function and quality of life of patients; it has also become one of the popular research topics in clinical trials. This paper summarizes the current clinical interventions and treatments of ACLF, including the clinical trials, therapeutic mechanisms, and research progress on MSC application in the treatment of ACLF. The problems and challenges of the development of MSC-based therapy in the future are also discussed.

Organ and tissue transplantation are limited by the scarcity of donated organs or tissue sources. The success of transplantation is limited by the risk of disease transmission and immunological- related rejection. There is a need for new strategies and innovative solutions to make transplantation readily available, safer and with less complications to increase the success rates. Accelerating progress in stem cell biology and biomaterials development have pushed tissue and organ engineering to a higher level. Among stem cells repertoire, Mesenchymal Stem Cells (MSC) are gaining interest and recognized as a cell population of choice. There is accumulating evidence that MSC growth factors, its soluble and insoluble proteins are involved in several key signaling pathways to promote tissue development, cellular differentiation and regeneration. MSC as multipotent non-hematopoietic cells with paracrine factors is advantageous for regenerative therapies. In this review, we discussed and summarized the important features of MSC including its immunomodulatory properties, mechanism of homing in the direction of tissue injury, licensing of MSC and the role of MSC soluble factors in cell-free therapy. Special consideration is highlighted on the rapidly growing research interest on the roles of MSC in ocular surface regeneration.

The liver is a vital organ for life and the only internal organ that is capable of natural regeneration. Although the liver has high regeneration capacity, excessive hepatocyte death can lead to liver failure. Various factors can lead to liver damage including drug abuse, some natural products, alcohol, hepatitis, and autoimmunity. Some models for studying liver injury are APAP-based model, Fas ligand (FasL), D-galactosamine/endotoxin (Gal/ET), Concanavalin A, and carbon tetrachloride-based models. The regeneration of the liver can be carried out using umbilical cord blood stem cells which have various advantages over other stem cell types used in liver transplantation. UCB-derived stem cells lack tumorigenicity, have karyotype stability and high immunomodulatory, low risk of graft versus host disease (GVHD), low risk of transmitting somatic mutations or viral infections, and low immunogenicity. They are readily available and their collection is safe and painless. This review focuses on recent development and modern trends in the use of umbilical cord stem cells for the regeneration of liver fibrosis.

Osteoarthritis (OA), as a degenerative joint disease, is the most common form of joint disorder that causes pain, stiffness, and other symptoms associated with OA. Various genetic, biomechanical, and environmental factors have a relevant role in the development of OA. To date, extensive efforts are currently being made to overcome the poor self-healing capacity of articular cartilage. Despite the pivotal role of chondrocytes, their proliferation and repair capacity after tissue injury are limited. Therefore, the development of new strategies to overcome these constraints is urgently needed. Recent advances in regenerative medicine suggest that pluripotent stem cells are promising stem cell sources for cartilage repair. Pluripotent stem cells are undifferentiated cells that have the capacity to differentiate into different types of cells and can self-renew indefinitely. In the past few decades, numerous attempts have been made to regenerate articular cartilage by using induced pluripotent stem cells (iPSCs). The potential applications of patient-specific iPSCs hold great promise for regenerative medicine and OA treatment. However, there are different culture conditions for the preparation and characterization of human iPSCs-derived chondrocytes (hiChondrocytes). Recent biochemical analyses reported that several paracrine factors such as TGFb, BMPs, WNT, Ihh, and Runx have been shown to be involved in cartilage cell proliferation and differentiation from human iPSCs. In this review, we summarize and discuss the paracrine interactions involved in human iPSCs differentiation into chondrocytes in different cell culture media.

Bone Marrow Mesenchymal Stem Cells (BMSCs) are one of the primary cells found in the bone marrow, and they can differentiate into osteoblasts, chondrocytes, adipocytes and even myoblasts, and are, therefore, considered pluripotent cells. Because of their multipotential differentiation, selfrenewal capability, immunomodulation and other potential activities, BMSCs have become an important source of seed cells for gene therapy, tissue engineering, cell replacement therapy and regenerative medicine. Long non-coding RNA (lncRNA) is an RNA molecule greater than 200 nucleotides in length that is expressed in a variety of species, including animals, plants, yeast, prokaryotes, and viruses, but lacks an apparent open reading frame, and does not have the function of translation into proteins. Many studies have shown that lncRNAs play an important role in the osteogenic differentiation of BMSCs. Here, we describe the role of lncRNAs in the osteogenic differentiation of BMSCs, in order to provide a new theoretical and experimental basis for bone tissue engineering and clinical treatment.

Transplantation of hematopoietic stem cells (HSCs) derived from umbilical cord blood (UCB) has been taken into account as a therapeutic approach in patients with hematologic malignancies. Unfortunately, there are limitations concerning HSC transplantation (HSCT), including (a) low contents of UCB-HSCs in a single unit of UCB and (b) defects in UCB-HSC homing to their niche. Therefore, delays are observed in hematopoietic and immunologic recovery and homing. Among numerous strategies proposed, ex vivo expansion of UCB-HSCs to enhance UCB-HSC dose without any differentiation into mature cells is known as an efficient procedure that is able to alter clinical treatments through adjusting transplantation-related results and making them available. Accordingly, culture type, cytokine combinations, O2 level, co-culture with mesenchymal stromal cells (MSCs), as well as gene manipulation of UCB-HSCs can have effects on their expansion and growth. Besides, defects in homing can be resolved by exposing UCB-HSCs to compounds aimed at improving homing. Fucosylation of HSCs before expansion, CXCR4-SDF-1 axis partnership and homing gene involvement are among strategies that all depend on efficiency, reasonable costs, and confirmation of clinical trials. In general, the present study reviewed factors improving the expansion and homing of UCB-HSCs aimed at advancing hematopoietic recovery and expansion in clinical applications and future directions.

Renal disease is a major worldwide public health problem that affects one in ten people. Renal failure is caused by the irreversible loss of the structural and functional units of kidney (nephrons) due to acute and chronic injuries. In humans, new nephrons (nephrogenesis) are generated until the 36th week of gestation and no new nephron develops after birth. However, in rodents, nephrogenesis persists until the immediate postnatal period. The postnatal mammalian kidney can partly repair their nephrons. The kidney uses intrarenal and extra-renal cell sources for maintenance and repair. Currently, it is believed that dedifferentiation of surviving tubular epithelial cells and presence of resident stem cells have important roles in kidney repair. Many studies have shown that stem cells obtained from extra-renal sites such as the bone marrow, adipose and skeletal muscle tissues, in addition to umbilical cord and amniotic fluid, have potential therapeutic benefits. This review discusses the main mechanisms of renal regeneration by stem cells after a kidney injury.

Stem cells play an essential role in maintaining homeostasis, as well as participating in new tissue regeneration. Over the past 20 years, a great deal of effort has been made to investigate the behaviour of stem cells to enable their potential use in regenerative medicine. However, a variety of biological characteristics are known to exist among the different types of stem cells due to variations in the methodological approach, formulation of cell culture medium, isolation protocol and cellular niches, as well as species variation. In recent years, cell-based therapy has emerged as one of the advanced techniques applied in both medical and clinical settings. Cell therapies aim to treat and repair the injury sites and replace the loss of tissues by stimulating the repair and regeneration process. In order to enable the use of stem cells in regenerative therapies, further characterisation of cell behaviour, in terms of their proliferation and differentiation capacity, mainly during the quiescent and inductive state is regarded as highly necessary. The central focus of regenerative medicine revolves around the use of human cells, including adult stem cells and induced pluripotent stem cells for cell-based therapy. The purpose of this review was to examine the existing body of literature on stem cell research conducted on cellular angiogenesis and migration, to investigate the validity of different strategies and variations of the cell type used. The information gathered within this review may then be shared with fellow researchers to assist in future research work, engaging in stem cell homing for cell-based therapy to enhance wound healing and tissue regeneration process.