Current Stem Cell Research & Therapy - Volume 17, Issue 5, 2022

Chimeric antigen receptor (CAR) T-cell therapy is a type of sophisticated tailored immunotherapy used to treat a variety of tumors. Immunotherapy works by utilizing the body's own immune system to discover and destroy malignant cells. In CAR-T therapy, a patient’s own immune cells are genetically engineered to recognize and attack cancer. Treatments employing CAR T-cells are currently showing promising therapeutic results in patients with hematologic malignancies, and their safety and feasibility in solid tumors have been verified. In this review, we will discuss in detail the likelihood that CAR Tcells inhibit cancer stem cells (CSCs) by selectively targeting their cell surface markers will ultimately improve the therapeutic response for patients with various forms of cancer. This review addresses the major components of cancer stem cell (CSC)-targeted CAR T-cells against malignancies, from bench to bedside.

Hematopoietic stem cells (HSCs) have self-renewal as well as pluripotency properties and are responsible for producing all types of blood cells. These cells are generated during embryonic development and transit through various anatomical niches (bone marrow microenvironment). Today, they are easily enriched from some sources, including peripheral blood, bone marrow, and umbilical cord blood (UCB). HSCs have been used for many years to treat a variety of cancers and blood disorders such as various types of leukemia, lymphoma, myelodysplastic, myeloproliferative syndromes, etc. Although almost 50 years have passed since the discovery of stem cells and numerous investigations on cell therapy and regenerative medicine have been made, further studies need to be conducted in this regard. This manuscript review the history, location, evolution, isolation, and therapeutic approaches of HSCs.

For many years, discovering the appropriate methods for the treatment of skin irritation has been challenging for specialists and researchers. Bio-printing can be extensively applied to address the demand for proper skin substitutes to improve skin damage. Nowadays, to make more effective biomimicry of natural skin, many research teams have developed cell-seeded bio-inks for bioprinting of skin substitutes. These loaded cells can be single or co-cultured in these structures. The present review gives a comprehensive overview of the methods, substantial parameters of skin bioprinting, examples of in vitro and in vivo studies, and current advances and challenges in skin tissue engineering.

Gastric cancer (GC) is the leading cause of death and cancer mortality in the world, with poor survival for cases with higher stages of GC. During the past decade, GC stem cells (GCSCs), a group of cancer cells, have been the focus of significant research on cancer. GCSCs have the capability of selfrenewal and are identified to participate in GC development, invasion, chemoresistance, and tumor relapse. Research projects have indicated the main activities of noncoding RNAs in cellular pathways. Micro (mi)RNAs and lncRNAs play important functions in the modulation of different cellular pathways in the post-transcriptional form through their dysregulated expression in several cancers, including GC. In this paper, we highlight the impact of dysregulated expression of micro- and lncRNAs and their downstream transcripts on GCSCs. Data collection on the progression of GCSCs may be beneficial for the introduction of new insights to the GC treatment.

Objective: The objective of this study is to analyze the efficacy and complications of regenerative medicine compared to autogenous bone graft for alveolar cleft reconstruction. Method: Electronic search was done through PubMed, Scopus, Embase and Cochrane databases for the studies published until May 2021. No limitations were considered for the type of the included studies. The risk of bias (ROB) of the studies was assessed using the Cochrane Collaborations and NIH quality assessment tool. Meta-analyses were performed to assess the difference in the amount of bone formation and rate of complications. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for analyzing the level of the evidence. Results: Among a total of 42 included studies, 21 studies used growth factors, 16 studies delivered cells, and five studies used biomaterials for bone regeneration of the alveolar cleft. Results showed no significant difference in the amount of bone formation between bone morphogenic protein-2 and iliac graft treated patients after six months (P = 0.44) and 12 months (P = 0.17) follow-up. Besides, higher swelling (OR=9.46, P < 0.01) and less infection (OR=0.19, P = 0.01) were observed in BMP treated patients. Using stem cells can reduce the post-treatment pain (OR=0.04, P = 0.01), but it has no significant impact on other complications (P > 0.05). Using tissue engineering methods reduced the operation time (SD=1.06, P < 0.01). GRADE assessment showed that results regarding the amount of bone formation volume after six and 12 months have low level of evidence. Conclusion: Tissue engineering methods can provide a comparable amount of bone formation to the autogenous graft and reduce some of the complications, operation time and hospitalization duration.

Background: The migration and differentiation of stem cells take place during the reparative phase of the healing cascade. Chemokine ligands and receptors are the key players in the homing process during the early stage of capillary morphogenesis. Stem cells from exfoliated deciduous teeth are known to possess a huge potential benefit for tissue regeneration. However, the gene expression of SHED engaging in angiogenesis and migratory activity during tissue healing is not fully understood. This study aims to assess the gene expression of SHED following in-vitro angiogenesis and migratory induction protocol. Methods: Scratch test assay was conducted following an angiogenic induction of SHED by supplementation of EGM-2 and VEGF. For the detection of migratory cell markers, angiogenic markers, and stem cell markers, RNA samples were extracted on days 1, 3, 7, 10, and 14 after the angiogenic induction in a transwell chamber, followed by RT-PCR analysis. Results: The findings suggested that SHED formed endothelial cells at higher capacity under an immature state with higher seeding density. SHED undergoing angiogenesis and migratory activity showed elevated IL-8, CCR1, CXCR4, and CCL28 expression. CCR1 expression significantly increased in the A+M+ group (p<0.05). Conclusion: The gene expression of these chemokines, particularly CCR1, which closely represent cellular migration, suggests the potential use of SHED for cell-based therapy to enhance tissue repair.

Background: While bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been used for many years in bone tissue engineering applications, the procedure still has drawbacks such as painful collection methods and damage to the donor site. Dental pulp-derived stem cells (DPSCs) are readily accessible, occur in high amounts, and show a high proliferation and differentiation capability. Therefore, DPSCs may be a promising alternative for BM-MSCs to repair bone defects. Objective: The aim of this study was to investigate the bone regenerative potential of DPSCs in comparison to BM-MSCs in vitro and in vivo. Methods: In vitro investigations included analysis of cell doubling time as well as proliferation and osteogenic differentiation. For the in vivo study, 36 male NMRI nude mice were randomized into 3 groups: 1) control (cell-free mineralized collagen matrix (MCM) scaffold), 2) MCM + DPSCs, and 3) MCM + BMMSCs. Critical size 2 mm bone defects were created at the right femur of each mouse and stabilized by an external fixator. After 6 weeks, animals were euthanized, and microcomputed tomography scans (μCT) and histological analyses were performed. Results: In vitro DPSCs showed a 2-fold lower population doubling time and a 9-fold higher increase in proliferation when seeded onto MCM scaffolds as compared to BM-MSCs, but DPSCs showed a significantly lower osteogenic capability than BM-MSCs. In vivo, the healing of the critical bone defect in NMRI nude mice was comparable among all groups. Conclusion: Pre-seeding of MCM scaffolds with DPSCs and BM-MSCs did not enhance bone defect healing.