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Fulltext Epithelial-mesenchymal plasticity-engaging stemness in an interplay of phenotypes

Chin VL, Lim CL

Stem Cell Investig, 2019;6:25.
PMID: 31559312 DOI: 10.21037/sci.2019.08.08

Cancer is a genetic disease which results in a functional imbalance between tumour-repressive and oncogenic signals. The WHO highlights the burden of this indomitable disease, listing it as the second leading cause of death globally. The major cause of cancer-related death is rarely the effect of the primary tumour itself, but rather, the devastating spread of cancer cells in metastases. Epithelial-mesenchymal plasticity (EMP)-termed as the ability of cells to maintain its plasticity and transit between epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states-plays a fundamental role in cancer metastasis. These cell transitions allow them migrate from the primary tumour and invade the secondary site. EMP is associated with migration, invasion, colonisation, self-renewal and drug resistance. This review briefly elucidates the mechanism of EMP and the association between cancer stem cells (CSCs) and circulating tumour cells (CTCs), biomarkers and signalling pathways involved in EMP as well as drug resistance and therapeutic targeting.
Fulltext Roles and mechanisms of stem cell in wound healing

Ayavoo T, Murugesan K, Gnanasekaran A

Stem Cell Investig, 2021;8:4.
PMID: 33829056 DOI: 10.21037/sci-2020-027

Wound healing phases comprise of highly synchronized process that begins due to a damage and restores the integrity of the injured tissues. Wound healing reduces the damage in tissue and supply sufficient oxygen and tissue perfusion, provide proper nourishment and humid wound healing atmosphere to re-establish the essential status of exaggerated parts. The untreated wound becomes susceptible for pus development, bacterial infection and complications like sepsis. Traditional and modern approaches are in practice to treat acute, open and chronic injuries, however, present wound care management has met with challenges and minimal positive effects. Stem cells have possible wound healing capability to overwhelm restrictions of the current wound care practices as it produces faster tissue regeneration in wound repair. Stem cells are unspecialized cells derived from adult body tissues and embryos that differentiate into any cell of an organism and capable of self-regeneration. The understanding on molecular mechanisms of stem cells has become the central and promising field in scientific study. This review focuses on the pre-existing traditional and modern treatments for wound healing, and types and roles of stem cells in wound care management. This review also focuses on the fundamental molecular characterization and factors influencing the molecular mechanisms of stem cells in wound healing.
Synergistic effects of intracoronary infusion of autologous bone marrow-derived mesenchymal stem cells and revascularization procedure on improvement of cardiac function in patients with severe ischemic cardiomyopathy

Chin SP, Maskon O, Tan CS, Anderson JE, Wong CY, Hassan HHC, et al.

Stem Cell Investig, 2021;8:2.
PMID: 33575315 DOI: 10.21037/sci-2020-026

Background: Ischemic cardiomyopathy (ICM) is a leading cause of cardiovascular mortality worldwide. It is defined as abnormal enlargement of the left ventricular (LV) cavity with poor LV function due to coronary artery disease. Currently available established treatments are palliative whereby blood supply is recovered to ischemic regions but fails to regenerate heart tissues. Mesenchymal stem cells (MSCs) offer a promising treatment for ICM given their regenerative and multipotent characteristics. This study aims to investigate the effect of MSCs infusion with concurrent revascularization in patients with severe ICM compared to receiving only revascularization procedure or MSCs infusion.
Methods: Twenty-seven patients with history of anterior myocardial infarction (MI) and baseline left ventricular ejection fraction (LVEF) of less than 35% were recruited into this study. Patients who are eligible for revascularization were grouped into group A (MSCs infusion with concurrent revascularization) or group B (revascularization only) while patients who were not eligible for revascularization were allocated in group C to receive intracoronary MSCs infusion. LV function was measured using echocardiography.
Results: Patients who received MSCs infusion (either with or without revascularization) demonstrated significant LVEF improvements at 3, 6 and 12 months post-infusion when compared to baseline LVEF within its own group. When comparing the groups, the magnitude of change in LVEF from baseline for third visits i.e., 12 months post-infusion was significant for patients who received MSCs infusion plus concurrent revascularization in comparison to patients who only had the revascularization procedure.
Conclusions: MSCs infusion significantly improves LV function in ICM patients. MSCs infusion plus concurrent revascularization procedure worked synergistically to improve cardiac function in patients with severe ICM.
Fulltext Safety and therapeutic potential of human bone marrow-derived mesenchymal stromal cells in regenerative medicine

Aithal AP, Bairy LK, Seetharam RN

Stem Cell Investig, 2021;8:10.
PMID: 34124233 DOI: 10.21037/sci-2020-036

Regenerative medicine is considered as an alternative approach to healthcare. Owing to their pluripotent abilities and their relative lack of ethical and legal issues, adult stem cells are considered as optimal candidates for use in the treatment of various diseases. Bone marrow-derived mesenchymal stem cells are among the most promising candidates for clinical applications as they have expressed a higher degree of plasticity in vitro. Many investigators have begun to examine how bone marrow stem cells might be used to rebuild damaged tissues. The systemic administration of cells for therapeutic applications requires efficient migration and homing of cells to the target site. Cell adhesion molecules and their ligands, chemokines, extracellular matrix components and specialized bone marrow niches all participate in the proper regulation of this process. MSCs suppress the pathophysiological process that is mediated by chronic inflammation and contributes to a modification of the microenvironment and tissue regeneration. Due to the intricacy of the mesenchymal stem cell, there is ever-increasing amount of data emerging about their migration and regenerative mechanisms. Many factors influence MSC mobilization and their homing to injured tissues. This review summarizes the current clinical and pre-clinical data available in literature regarding the use of MSC in tissue repair and their prospective therapeutic role in various diseases and the underlying repair mechanisms will be discussed.
Targeting Notch signalling pathway of cancer stem cells

Venkatesh V, Nataraj R, Thangaraj GS, Karthikeyan M, Gnanasekaran A, Kaginelli SB, et al.

Stem Cell Investig, 2018;5:5.
PMID: 29682512 DOI: 10.21037/sci.2018.02.02

Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. CSCs have been increasingly identified in blood cancer, prostate, ovarian, lung, melanoma, pancreatic, colon, brain and many more malignancies. CSCs have slow growth rate and are resistant to chemotherapy and radiotherapy that lead to the failure of traditional current therapy. Eradicating the CSCs and recurrence, is promising aspect for the cure of cancer. The CSCs like any other stem cells activate the signal transduction pathways that involve the development and tissue homeostasis, which include Notch signaling pathway. The new treatment targets these pathway that control stem-cell replication, survival and differentiation that are under development. Notch inhibitors either single or in combination with chemotherapy drugs have been developed to treat cancer and its recurrence. This approach of targeting signaling pathway of CSCs represents a promising future direction for the therapeutic strategy to cure cancer.
Breast cancer stem cells-from origins to targeted therapy

Sin WC, Lim CL

Stem Cell Investig, 2017;4:96.
PMID: 29270422 DOI: 10.21037/sci.2017.11.03

Breast cancer is marked as one of the leading causes of malignancy-related morbidities worldwide. In spite of aggressive interventions, the inevitability of relapse and metastasis severely impede survival rates. Mounting evidence highlight the insidious role of cancer stem cells (CSCs), a small but significant subpopulation of undifferentiated cells that drive tumour progression, spread and resistance to conventional therapy. The nature and significance of breast CSCs remains poorly understood, and even disputed by many researchers. This review discusses the origins, biomarkers, signalling pathways, regulatory mechanisms, and targeted therapy of breast CSCs.