Current Stem Cell Research & Therapy - Volume 10, Issue 6, 2015

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease resulting from multiplex causes. Evidence indicates that stem/progenitor cells might play a key role in IPF pathogenesis and repair, which may provide some novel potential strategies for the future treatment of IPF. In this review, we first summarize the current understanding of the relationship between stem cells and IPF and then review the advancements made in recent clinical trials using stem/progenitor cells, especially mesenchymal stem cells, in treating IPF and their interpretations.

Differentiating embryonic stem cells into a specific lineage or cell type is one of the most investigated areas of stem cell research; however it is wrought with hurdles. The differentiation process during embryogenesis is greatly influenced by physiochemical factors. They direct key genes for lineage commitment, which in turn are responsible for patterning into highly organized tissues resulting in organ formation. In this review, we have focused on the influence of physiochemical factors on the differentiation process in embryonic stem cells, which mimics, embryogenesis in vivo.

Acquired immunodeficiency syndrome (AIDS), an infectious disease which is difficult to be cured, is regularly and effectively treated with anti-retroviral therapy in clinic. When considering about the defects of antiretroviral therapy (ART), patients need a new way to cure AIDS. With the development of genetic engineering technology and humanized mouse models, a new way has been found to achieve a “functional cure” for AIDS. One/some specific gene(s), such as CCR5 and CXCR4, can be knocked out to produce HIV-resisting cells, so as to achieve the purpose of curing AIDS. To find a safe and effective therapy for AIDS, treatment strategy and technical scheme should be improved and optimized in many aspects. Moreover, different stages of works have been done in laboratory and in clinic based on this gene mutation strategy. However, a great deal of challenge has emerged while great progress has been made. Safety considerations and effectiveness of gene modified stem cell in clinic are major obstacles of the application of this strategy.

Inflammatory Bowel Disease (IBD) is a complicated disease that arises as a consequence of the interaction among environment, genetic factors and autoimmunity. Available therapeutic interventions with pharmacological or biological drugs have a very selective action. Mesenchymal stem cells (MSCs) have been emerging as a promising cellular therapy for the treatment of IBD due to their multifaceted functions. This article summarizes recent progress in both preclinical studies and clinical trials employing MSCs in IBD treatment. We justify the use of MSC-based cell therapy as a novel strategy for IBD, discuss the biological roles that MSCs play underlying their therapeutic effects focusing on their immune-suppressive effects, illustrate methods to improve MSCs for better repair, and pinpoint the obstacles hindering their success and the challenges to overcome before their ultimate application.

The processes of new vessels formation in tissues are supported by two definite mechanisms: de novo development of blood vessels (vasculogenesis) through the accumulation of progenitor cells during early prenatal stage, and extension of a pre-existing microcirculatory network by endothelial cell germination (angiogenesis), the essential mechanism of blood vessel formation in postnatal period. Angiogenesis is associated with a series of inductive, permissive and restrictive communications that result in the appearance, differentiation, and formation of new vessels. The goal of therapeutic angiogenesis is to improve blood circulation, relay survival factors and regenerative stem cell populations to sites of tissue repair, and ultimately recover function and form of the tissue. Growth factors and bone marrow mononuclear cells represent a very interesting research field for the realization of therapeutic angiogenesis in ischemic tissues. They provide a potential key component in the healing processes of ischemic injured tissues.

Tumors grow in privileged microenvironment referred to as the cancer niche. This niche is composed of cancer cells and various components including mesenchymal stem cells (MSC), fibroblasts, network of microvasculature added to innate and primed immune cells. Additionally, it encloses other elements such as the extracellular matrix (ECM), cytokines, chemokines and growth factors. Crosstalk between cancer cells and different niche constituents is crucial for tumor growth and metastasis. Herein, we focus attention on the bidirectional relationship between MSC and cancer cells and its impact on tumor progression. Better comprehension of these events within the tumor niche might be valuable for developing effective anti-tumor therapeutic strategies.

Mesenchymal stem cells (MSCs) play an important role in embryonic development and tissue regeneration in adult life owing to their high competency and self-renewal features. MSCs represent an important stem cell population with multipotent capabilities that may have high utility for translational clinical applications. MSCs can differentiate into a variety of cell types, especially fascia originated cells, and provide soluble factors for regeneration of tissues and organs. In in vitro environments, stem cells are capable of reproducing while preserving their properties; therefore, assuming stem cells could be reproduced in sufficient quantity, they would be appropriate for genetic operations. Stem cells can be used in tissue engineering, preventing rejection of bone marrow/ stem cell grafts by supporting hematopoiesis and recovery of autoimmune diseases, and cell therapy through their immunosuppressive properties. Mesenchymal stem cells have the potential capability to renew deformed organs and assist in tissue repair. In the field of wound healing, use of BM-MSCs is effective through modulating inflammation, extracellular matrix production, migration of keratinocytes, and angiogenesis for cell therapies. A significant complication of diabetes is diabetic foot ulcers, which affect quality of life and threaten life. In this article, we review recent studies with favorable results related to MSCs, which have become an important area of study in terms of tissue regeneration and regenerative medicine with diabetic foot ulcers.

Arthroscopic anterior cruciate ligament (ACL) reconstruction using tendon grafts is the current gold standard for the treatment of ACL tears in active patients. However, many patients still experience residual knee instability, knee pain and progressive cartilage degeneration following ACL reconstruction. Recent developments in mesenchymal stem cell (MSC)-based approaches for treating musculoskeletal injuries have led to the application of MSCs for enhancing healing after ACL injuries. The purpose of this article is to review recent pre-clinical and clinical studies using MSCs for the enhancement of biologic healing of ACL injuries. Because of the success of pre-clinical studies, MSC-based approaches are now thought to be promising treatment options for enhancing biologic healing of ACL grafts and restoring the functional properties to the levels of the native ACL, and ultimately improving clinical outcomes.