Current Stem Cell Research & Therapy - Volume 12, Issue 1, 2017

Inadequate blood supply frequently impedes the viability of tissue-engineered constructs in the initial phase after implantation, and can lead to improper cell integration or cell death. Vascularization using stem cells has continued to evolve as a potential solution to this problem. In this review, we summarize studies that utilize endothelial progenitor cells (EPCs) for musculoskeletal regeneration. This review will also highlight recent concepts for EPC identification in conjunction with the development of EPC biology research. EPCs promote bone regeneration in animal models through a variety of mechanisms. By differentiating toward endothelial cell lineages and osteoblasts, EPCs stimulate vasculogenesis, angiogenesis and osteogenesis. Moreover, EPCs influence supporting cells through the secretion of growth factors and cytokines. Phase I/II clinical trials have applied circulating CD34+ cells/EPCs to nonunion bone fractures and have exhibited promising results including accelerated bone healing. Similar mechanisms of angiogenesis and osteogenesis are proposed for anterior cruciate ligament (ACL) ruptured tissue derived CD34+ cells, and thus EPCs have implied a critical role at the site of tendon-bone integration. EPCs are an emerging strategy among other cell-based therapies in the field of orthopaedics for the promotion of musculoskeletal regeneration.

Since the improvement of chemotherapy and innovation of rituximab, about 60% of patients with diffuse large B cell lymphoma (DLBCL) could receive long-term survival after firstline therapy. Around 30% fail to respond or experience relapse considered as the relapsed/refractory DLBCL, the highdose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) has been used as the second-line treatment. However, the patients relapse after auto-HSCT or not eligible for the auto-HSCT have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the potentially curative way in such kind of patients. In this paper, we collected the published data about patients with relapsed/refractory DLBCL who underwent allo-HSCT, demonstrated the appropriate candidate for allo-HSCT, identified the effect of the donor types on the recipients, presented the major conditioning regimens for allo-HSCT and figured out the outcomes of each conditioning regimen. We also tried to identify the prognostic factors on the outcome which might shed some light on the further clinical application.

In the last decade, an increasing number of studies on tumor stem cell theory stating that there is only a small fraction of tumor cells capable of inducing tumor growth have been published. These cells can not only differentiate into more mature tumor cells, but also can maintain their own pool, that is the capacity for self-renewal. There are distinct subpopulations of cells within a tumor that express different combinations of stem cell markers and have different functions. The following markers are typically considered as markers of colorectal adenocarcinoma stem cells: CD133, CD144, CD24, CD166, CD44, CD29, ALDH1, LGR5, and CXCR4. However, data on the role of cancer stem cells in the process of colorectal cancer progression, their prognostic and predictive role are lacking. Researches on the phenotype, molecular and functional properties of this tumor cell subpopulation in both primary site and metastases of colorectal cancer are of great interest because they can allow developing new diagnostic and therapeutic strategies in the future.

Exosomes and microvesicles, which are released by most of the cells, play important roles in intracellular correspondence by transferring DNA, messenger RNA, micro RNA, and other types of RNA and proteins. Exosomes and microvesicles may contribute to the distribution of cancers and diseases through delivering the pathogenic agents to the non-infected cells; in cancers, they can modify the cells in the tumor niche and lead them to transformation. In addition, these vesicles can affect stem cell activity and their physiological properties. On the other hand, exosomes and microvesicles can be applied in the therapeutic strategies as they are small, non-viral, flexible and able to cross biological barriers. In this review, we focused on some details about the exosomes and microvesicles both functionally and structurally.

The identification of Cancer Stem Cells (CSCs) in leukemia has opened a new field in cancer research. This has led to the identification of similar cells in other types of cancer. CSCs express distinct surface markers and functional properties which distinguish them from the rest of the cells within a tumor. Due to variability in identification of CSCs in a particular type of cancer (except brain, breast and leukemia), surface markers alone may not be sufficient. It is critical to identify and isolate this small population of cells from the heterogeneous tumors to understand their pathogenesis. Identification of surface markers together with intrinsic properties of CSCs like colony formation, Hoechst exclusion or ALDEFLUOR assay may be useful in isolating more primitive and highly pure CSCs from a heterogeneous population of malignant cells. This review critically analyses various techniques and methods along with their advantages and disadvantages that are employed in identifying CSCs from different types of cancers.

Regulation (EC) 1394/2007 of the European Parliament and the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 allowed the use of non - authorized advanced therapy medicinal products under the certain circumstances. This socalled hospital exemption rule needs to be applied in the each Member State of the European Union individually and for this purpose Member States should provide national procedures and control measures. The aim of this article is to clear up the criteria for hospital exemption listed in Regulation (EC) 1394/2007 and to contrast the difference in implementing hospital exemption rule into national legal regimes on examples of the United Kingdom, Lithuania and Poland.

Oral mucosa is a mucous membrane lining the oral cavity. Its main function is to protect the deeper structures against the external factors; thermal, chemical, mechanical and biological stimuli. Apart from that, it also plays a significant role during mastication, deglutition and speech. Some oral diseases or injuries to oral mucosa lead to impairment of the oral functions and aesthetics which eventually result in permanent defect of oral mucosa. In order to overcome this defect, different approaches for the development of reconstructed oral mucosa models have been employed including skin/autologous grafts, guided tissue replacement, vestibuloplasty etc. However, the finding of an acceptable source for the transplantations or autologous grafts seems a bit challenging. To overcome this problem, the development of oral mucosa using tissue engineering approach has been widely studied involving various cell lines from different sources. This paper aims to highlight various cell sources used in the development of tissueengineered oral mucosa models based on articles retrieved from PubMed and MEDLINE databases using the search terms “oral mucosa tissue engineering”, regardless of time when published.

In this review we explore stem cell function in wounds that are resistant to healing, such as burn injuries and diabetic wounds. Diabetic ulcers are of interest due to their remarkable resistance to heal; severe thermal burns are addressed due to critical need for effective therapies for the prevention shock and improvement in scarring. Cell-based therapy utilizing mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, are currently being investigated as a therapeutic avenue for both chronic diabetic ulcers and severe thermal burns. The clinical utility of stem cells, in particular MSCs, in caring for these types of injuries is primarily based on repairing and replacing cellular substrates, attenuation of inflammation, increasing angiogenesis, and enhancing migration of reparative cells. MSCs are sought after due to their unique ability to initiate different wound-healing programs, depending on the environmental milieu. Thus, this review aims to highlight the properties of MSCs, including their characterization, immunogenicity, and function in the context of dermal repair and regeneration in severe burns and diabetic wounds. Additionally, relevant clinical and pre-clinical studies illustrating the impact of allogeneic and autologous sources of MSCs on therapeutic efficacy are reviewed. Insight into the properties of MSCs and the dramatic host-to-MSC interactions within these pathological states may lead to the development of effective strategies for improving outcomes in impaired wounds.

The odontogenic and osteogenic potential of dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous tooth (SHED) have been shown clearly by various in vitro and in vivo studies. The findings are promising and demonstrated that dental tissue engineering can give a new hope to the individuals suffering from tooth loss and dental diseases. The evaluation of odontogenic and osteogenic differentiation of DPSCs and SHED is commonly carried out by an illustration of the expression of varied related markers. In this review, few commonly used markers such as alkaline phosphatase (ALP), collagen type 1 (Col I), dentin matrix acid phosphoprotein 1 (DMP1), dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE), osteocalcin (OCN), and osteopontin (OPN). DSPP, DMP1, and MEPE (odontogenic markers), which play an important role during early odontoblastic differentiation and late dentin mineralization, have been highlighted. Osteoblastic proliferation and early/late osteoblastic differentiation can be assessed by estimating the expression of Col I, ALP, OCN and OPN. Despite that, till date, there is no marker which could demonstrate for certain, the differentiation of human DPSCs and SHED towards the odontogenic and osteogenic lineage. This review suggests that SHED are noticeably different from DPSCs and exhibited higher capacity for osteogenic differentiation compared to DPSCs. On the other hand, different expression levels are shown by SHED and DPSCs with regards to the osteoblast markers for osteoblastic differentiation, where, SHED expressed higher levels of ALP, Col I and OCN compared to DPSCs.

Lung diseases cause great morbidity and mortality. The choice of effective medical treatment is limited and the number of lung diseases are difficult to treat with current treatments. The embryonic stem cells (ESCs) have the potential to differentiate into cell types of all three germinal layers, including lung epithelial cells. So they can be a potential source for new cell therapies for hereditary or acquired diseases of the airways and lungs. One method for treatment of lung diseases is cell therapy and the use of ESCs that can replace the damaged epithelial and endothelial cells. Progress using ESCs has developed slowly for lung regeneration because differentiation of lung cells from ESCs is more difficult as compared to differentiation of other cells. The review studies the therapeutic effects of differentiated lung cells from embryonic stem cells in lung diseases. There are few studies of differentiation of ESCs into a lineage of respiratory and then investigation of this cell in experimental model of lung diseases.