Current Stem Cell Research & Therapy - Volume 14, Issue 6, 2019

Asherman’s Syndrome or Intrauterine adhesions is an acquired uterine condition where fibrous scarring forms within the uterine cavity, resulting in reduced menstrual flow, pelvic pain and infertility. Until recently, the molecular mechanisms leading to the formation of fibrosis were poorly understood, and the treatment of Asherman’s syndrome has largely focused on hysteroscopic resection of adhesions, hormonal therapy, and physical barriers. Numerous studies have begun exploring the molecular mechanisms behind the fibrotic process underlying Asherman’s Syndrome as well as the role of stem cells in the regeneration of the endometrium as a treatment modality. The present review offers a summary of available stem cell-based regeneration studies, as well as highlighting current gaps in research.

Endothelial progenitor cells (EPCs) are implicated in multiple biologic processes such as vascular homeostasis, neovascularization and tissue regeneration, and tumor angiogenesis. A subtype of EPCs is referred to as endothelial colony-forming cells (ECFCs), which display robust clonal proliferative potential and can form durable and functional blood vessels in animal models. In this review, we provide a brief overview of EPCs’ characteristics, classification and origins, a summary of the progress in preclinical studies with regard to the therapeutic potential of human umbilical cord blood derived ECFCs (CB-ECFCs) for ischemia repair, tissue engineering and tumor, and highlight the necessity to select high proliferative CB-ECFCs and to optimize their recovery and expansion conditions.

Stem cells are unspecialized cells and excellent model in developmental biology and a promising approach to the treatment of disease and injury. In the last 30 years, pluripotent embryonic stem (ES) cells were established from murine and primate sources, and display indefinite replicative potential and the ability to differentiate to all three embryonic germ layers. Despite large efforts in many aspects of rodent and non-rodent pluripotent stem cell culture, a number of diverse challenges remain. Natural and synthetic small molecules (SMs) strategy has the potential to overcome these hurdles. Small molecules are typically fast and reversible that target specific signaling pathways, epigenetic processes and other cellular processes. Inhibition of the transforming growth factor-β (TGF-β/Smad) and fibroblast growth factor 4 (FGF4)/ERK signaling pathways by SB431542 and PD0325901 small molecules, respectively, known as R2i, enhances the efficiency of mouse, rat, and chicken pluripotent stem cells passaging from different genetic backgrounds. Therefore, the application of SM inhibitors of TGF-β and ERK1/2 with leukemia inhibitory factor (LIF) allows the cultivation of pluripotent stem cells in a chemically defined condition. In this review, we discuss recently emerging evidence that dual inhibition of TGF-β and FGF signaling pathways plays an important role in regulating pluripotency in both rodent and non-rodent pluripotent stem cells.

Aberrant or prolonged immune responses has been proved to be involved in bone homeostasis. As a component of the innate immune system, macrophages play a critical role in bone homeostasis. Conventionally, according to response to the various panel of stimuli, macrophages can be plastically classified into two major phenotypes: M1 and M2. M1 macrophages are generally proinflammatory, whereas M2 are anti-inflammatory. Although studies demonstrated that both M1 and M2 phenotypes have been implicated in various inflammatory bone diseases, their direct role in bone homeostasis remains unclear. Thus, in this review, we briefly discuss the term “osteoimmunology”, which deals with the crosstalk and shared mechanisms of the bone and immune systems. In addition, we overview M1 and M2 macrophages for their role in osteoclastogenesis and osteogenesis as well as relevant signaling cascades involved.

Background: Recent studies have shown the great value of cell therapy over the past few decades. Mesenchymal stem cells (MSCs) have been reported to treat various degenerative diseases not through their differentiation potential but through their paracrine factors of the extracellular vesicle (EV) including exosomes. Exosomes are nanosized (70~150 nm) membrane-bound extracellular vesicles, not only involved in cell-to-cell communication but also in the development of tissue injury repair. Objective: As more researchers proved the enormous potential of exosomes in the field of repairing damaged tissue currently, it is urgent to explore the concrete mechanism and make exosomes to be a practical treatment tool in clinical medicine. In our study, we analyzed and summarized the work on tissue repair via exosomes in order to give some suggestions about the application of exosomes in clinical reality in the future. Results: MSC-derived exosomes (MSC-Ex) contain a wide variety of functional proteins, mRNAs, miRNAs and signaling lipids. Compared with their parent cells, MSC-Ex are more stable and can reduce the inherent safety risks in administering viable cells such as the risk of occlusion in microvasculature. MSC-Ex can be used to develop a cell-free exosome-based therapy for regenerative medicine, and may provide an alternative to MSC-based therapy. Conclusion: This review summarizes the most recent knowledge of therapeutic potential of MSC-Ex in the liver, heart, kidney, bone, brain diseases and cancer, as well as their associated challenges and opportunities.

Spinal cord injury (SCI) is a devastating event, and there are still no effective therapies currently available. Neural stem cells (NSCs) have gained increasing attention as promising regenerative therapy of SCI. NSCs based therapies of various neural diseases in animal models and clinical trials have been widely investigated. In this review we aim to summarize the development and recent progress in the application of NSCs in cell transplantation therapy for SCI. After brief introduction on sequential genetic steps regulating spinal cord development in vivo, we describe current experimental approaches for neural induction of NSCs in vitro. In particular, we focus on NSCs induced from pluripotent stem cells (PSCs). Finally, we highlight recent progress on the NSCs, which show great promise in the application to regeneration therapy for SCI.

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords “ADIPOSE”, “CELLS”, and “PERIODONTAL”, with the Boolean operator “AND”. A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs.

Background: Numerous studies have defined the outstanding role of circulating tumor cells (CTC) in the management of cancer, particularly the ones in association with primary tumor metastases. Objective: The overall aim of the present study was to investigate whether CTCs may serve as a clinical prognostic marker for survival in primary breast cancer. Methods: Articles Published from June 2011 to July 2017 in PubMed, EMBase, and Cochrane library databases were thoroughly screened for selecting the ones meeting the inclusion criteria. Result: Studies applying CellSearch® method demonstrated the risk ratios (RR) of 2.51 (95% CI: 1.78- 3.54), 3.98 (95% CI: 2.28- 6.95), 5.59 (95% CI: 3.29- 9.51), and 3.38 (95% CI: 1.88- 6.06) for death rate and relapse rates of 2.48 (95% CI: 1.89 - 3.26), 3.62 (95% CI: 2.37 - 5.51), 4.45 (95% CI: 2.94 - 6.73), and 2.88 (95 % CI: 1.99 - 4.17) at four CTC positive cut points (≥ 1, ≥ 2, ≥ 3, and ≥ 5 CTCs/7.5 ml). Two studies applying the AdnaTest® also documented increased death (RR: 1.38, 95 % CI: 0.42- 4.49) and relapse rates (RR: 2.97, 95 % CI: 1.23 - 7.18)). Conclusion: Results of this meta-analysis allude CTCs as potent prognostic markers in primary breast cancers prior to any systemic therapy especially when it is studied via CellSearch® administration, considering that the more the CTCs, the greater the death and relapse rates.