Current Stem Cell Therapies Research Articles

Hydrogels in cardiac tissue engineering: application and challenges.

Cardiovascular disease remains the leading cause of global mortality. Current stem cell therapy and heart transplant therapy have limited long-term stability in cardiac function. Cardiac tissue engineering may be one of the key methods for regenerating damaged myocardial tissue. As an ideal scaffold material, hydrogel has become a viable tissue engineering therapy for the heart. Hydrogel can not only provide mechanical support for infarcted myocardium but also serve as a carrier for various drugs, bioactive factors, and cells to increase myocardial contractility and improve the cell microenvironment in the infarcted area, thereby improving cardiac function. This paper reviews the applications of hydrogels and biomedical mechanisms in cardiac tissue engineering and discusses the challenge of clinical transformation of hydrogel in cardiac tissue engineering, providing new strategies for treating cardiovascular diseases.

CRISPR-Cas9 immune-evasive hESCs are rejected following transplantation into immunocompetent mice.

Although current stem cell therapies exhibit promising potential, the extended process of employing autologous cells and the necessity for donor-host matching to avert the rejection of transplanted cells significantly limit the widespread applicability of these treatments. It would be highly advantageous to generate a pluripotent universal donor stem cell line that is immune-evasive and, therefore, not restricted by the individual's immune system, enabling unlimited application within cell replacement therapies. Before such immune-evasive stem cells can be moved forward to clinical trials, in vivo testing via transplantation experiments in immune-competent animals would be a favorable approach preceding preclinical testing. By using human stem cells in immune competent animals, results will be more translatable to a clinical setting, as no parts of the immune system have been altered, although in a xenogeneic setting. In this way, immune evasiveness, cell survival, and unwanted proliferative effects can be assessed before clinical trials in humans. The current study presents the generation and characterization of three human embryonic stem cell lines (hESCs) for xenogeneic transplantation in immune-competent mice. The major histocompatibility complexes I- and II-encoding genes, B2M and CIITA, have been deleted from the hESCs using CRISPR-Cas9-targeted gene replacement strategies and knockout. B2M was knocked out by the insertion of murine CD47. Human-secreted embryonic alkaline phosphatase (hSEAP) was inserted in a safe harbor site to track cells in vivo. The edited hESCs maintained their pluripotency, karyotypic normality, and stable expression of murine CD47 and hSEAP in vitro. In vivo transplantation of hESCs into immune-competent BALB/c mice was successfully monitored by measuring hSEAP in blood samples. Nevertheless, transplantation of immune-evasive hESCs resulted in complete rejection within 11days, with clear immune infiltration of T-cells on day 8. Our results reveal that knockout of B2M and CIITA together with species-specific expression of CD47 are insufficient to prevent rejection in an immune-competent and xenogeneic context.

Oral ulcer treatment using human tonsil-derived mesenchymal stem cells encapsulated in trimethyl chitosan hydrogel: an animal model study

BackgroundOral ulcers are a common side effect of chemotherapy and affect patients’ quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness.MethodsAnimals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect.ResultsThe ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups.ConclusionThis study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications.

Stem Cell Therapy for Liver Diseases: Current Perspectives.

Stem cell therapy offers a promising avenue for advanced liver disease cases as an alternative to liver transplantation. Clinical studies are underway to explore the potential of stem cells from various sources in treating different liver diseases. However, due to the variability among current studies, further validation is needed to ensure the safety and effectiveness of stem cell therapy. To establish a strong foundation for optimal stem cell therapy applications, selection of suitable stem cell sources, standardization of transplantation protocols, and patient criteria are vital. This review comprehensively examines existing literature on stem cell sources, transplantation methods, and patient selection. Additionally, we discuss novel strategies, including stem cell preconditioning, cell-free therapy, genetic modification of stem cells, and the use of liver organoids, addressing the limitations of current stem cell therapies. Nevertheless, these innovative approaches require further validation.

Stem cell therapies for ischemic heart disease: clinical trial outcomes and futures

Ischemic heart disease carries high morbidity and mortality despite modern pharmaceutical treatment and revascularization procedures. Biologic stem cell therapy offers the potential to revolutionize clinical outcomes for ischemic heart disease by reducing scarring and improving cardiac function. Several small randomized clinical trials have been done utilizing various methodologies, different types of stem cells and doses, and measuring different clinical outcomes. The findings of these individual studies, as well as larger meta-analyses, have been inconsistent likely due to the significant heterogeneity within the methods used. In this review, we provide a more structured approach by comparing the recent studies by type of disease, stem cells, dose, delivery method, and outcome in an effort to draw attention to the similarities and differences in these studies and the need for a standardized approach in larger trials. We show that out of all the current stem cell therapies that have been tried, Adult stem cells, primarily mesenchymal stem cells are currently the most promising for post-myocardial infarction and heart failure while granulocyte colony-stimulating factor and bone marrow mononuclear treatment show efficacy in treating ischemic cardiomyopathy. Lastly, we discuss the potential future directions of stem cell therapy for clinical application in ischemic heart disease.

Bibliometric and visual analysis of mesenchymal stem cells in the treatment of osteoporosis based on CiteSpace software.

The focus of research in the treatment of osteoporosis (OP) has evolved from promoting bone formation and inhibiting bone resorption to current stem cell therapy. Due to their multipotent differentiation properties, mesenchymal stem cells (MSCs) can repair degenerated bones through transplantation, and have become a new method for the treatment of OP. Relevant literatures included in the Web of Science database core collection database from 2012 to 2021 were retrieved. CiteSpace software was used to analyze the cooperative relationship among authors, journals, institutions, and countries, and to analyze the co-citation situation of the literature. And performed co-occurrence analysis, cluster analysis and burst analysis of keywords, draw visual maps and analyzed the results. A total of 2100 papers were included, and the number of papers published from 2012 to 2021 was on the rise. A total of 484 authors were included, and 176 authors published more than 3 papers. The high-yield authors were mainly represented by YAN JIN and BO GAO. A total of 99 journals were included, and the journal with the most publications was J BONE MINER RES. A total of 787 institutions were included, and the institution with the largest number of publications was Shanghai Jiao Tong University. A total of 65 countries were included. The country with the largest number of publications was China, and the United States had the highest centrality. The co-citation analysis of the literature found 2 articles with high citation frequency and high centrality. The main research direction was the mechanism of MSCs in the treatment of osteoporosis. A total of 133 keywords were included, and the hot keywords were osteogenic differentiation, expression, proliferation, bone marrow, etc. The research hotspots in this field mainly focused on the mechanism of bone regeneration, proliferation and osteogenic differentiation of bone marrow MSCs, and the expression of osteogenic-related genes. The future research trends in this field are predicted to be the mechanism of action of microRNA and long non-coding RNA on MSCs and their relationship with OP, the mechanism of MSCs adipogenic and osteogenic differentiation, and tissue engineering scaffolds applications.

Directional control of neurite outgrowth: emerging technologies for Parkinson's disease using magnetic nanoparticles and magnetic field gradients.

A challenge in current stem cell therapies for Parkinson's disease (PD) is controlling neuronal outgrowth from the substantia nigra towards the targeted area where connectivity is required in the striatum. Here we present progress towards controlling directional neurite extensions through the application of iron-oxide magnetic nanoparticles (MNPs) labelled neuronal cells combined with a magnetic array generating large spatially variant field gradients (greater than 20 T m-1). We investigated the viability of this approach in both two-dimensional and organotypic brain slice models and validated the observed changes in neurite directionality using mathematical models. Results showed that MNP-labelled cells exhibited a shift in directional neurite outgrowth when cultured in a magnetic field gradient, which broadly agreed with mathematical modelling of the magnetic force gradients and predicted MNP force direction. We translated our approach to an ex vivo rat brain slice where we observed directional neurite outgrowth of transplanted MNP-labelled cells from the substantia nigra towards the striatum. The improved directionality highlights the viability of this approach as a remote-control methodology for the control and manipulation of cellular growth for regenerative medicine applications. This study presents a new tool to overcome challenges faced in the development of new therapies for PD.

Immunomodulatory Effect and Bone Homeostasis Regulation in Osteoblasts Differentiated from hADMSCs via the PD-1/PD-L1 Axis.

Human mesenchymal stem cells (hMSCs) are promising candidates for stem cell therapy and are known to secrete programmed death-1 (PD-1) ligand 1 (PD-L1) regulating T cell-mediated immunosuppression. Given the limitations of current stem cell therapy approaches, improvements in immunomodulatory capacity and stem cell differentiation efficacy are needed. In this study, we propose novel strategies to overcome the challenges that remain in hMSC-mediated bone regeneration. We found that PD-1 is highly expressed in osteoblasts, and the PD-1/PD-L1 axis mediated the decreased proinflammatory cytokine expressions in differentiated osteoblasts cocultured with human adipose derived mesenchymal stem cells (hADMSCs). Moreover, the decrease was attenuated by PD-1/PD-L1 pathway inhibition. Osteogenic properties including osteogenic gene expression and calcium deposits were increased in osteoblasts cocultured with hADMSCs compared with those that were monocultured. Osteoblasts treated with PD-L1 and exosomes from hADMSCs also exhibited enhanced osteogenic properties, including calcium deposits and osteogenic gene expression. In our cocultured system that mimics the physiological conditions of the bone matrix, the PD-1/PD-L1 axis mediated the increased expression of osteogenic genes, thereby enhancing the osteogenic properties, while the calcium deposits of osteoblasts were maintained. Our results provide the therapeutic potentials and novel roles of the PD-1/PD-L1 axis in bone matrix for modulating the bone properties and immunosuppressive potentials that can aid in the prevention of bone diseases via maintaining bone homeostasis.

Enhanced osteoarthritis therapy by nanoengineered mesenchymal stem cells using biomimetic CuS nanoparticles loaded with plasmid DNA encoding TGF-β1.

Mesenchymal stem cells (MSCs) therapy shows the potential benefits to relieve clinical symptoms of osteoarthritis (OA), but it is uncertain if it can repair articular cartilage lesions — the main pathology of OA. Here, we prepared biomimetic cupper sulfide@phosphatidylcholine (CuS@PC) nanoparticles (NPs) loaded with plasmid DNA (pDNA) encoding transforming growth factor-beta 1 (TGF-β1) to engineer MSCs for enhanced OA therapy via cartilage regeneration. We found that the NPs not only promoted cell proliferation and migration, but also presented a higher pDNA transfection efficiency relative to commercial transfection reagent lipofectamine 3000. The resultant CuS/TGF-β1@PC NP-engineered MSCs (termed CTP-MSCs) were better than pure MSCs in terms of chondrogenic gene expression, glycosaminoglycan deposition and type II collagen formation, favoring cartilage repair. Further, CTP-MSCs inhibited extracellular matrix degradation in interleukin-1β-induced chondrocytes. Consequently, intraarticular administration of CTP-MSCs significantly enhanced the repair of damaged cartilage, whereas pure MSCs exhibited very limited effects on cartilage regeneration in destabilization of the medial meniscus (DMM) surgical instability mice. Hence, this work provides a new strategy to overcome the limitation of current stem cell therapy in OA treatment through developing more effective nanoengineered MSCs.

MiR-125 Family in Cardiovascular and Cerebrovascular Diseases.

Cardiovascular and cerebrovascular diseases are a serious threaten to the health of modern people. Understanding the mechanism of occurrence and development of cardiovascular and cerebrovascular diseases, as well as reasonable prevention and treatment of them, is a huge challenge that we are currently facing. The miR-125 family consists of hsa-miR-125a, hsa-miR-125b-1 and hsa-miR-125b-2. It is a kind of miRNA family that is highly conserved among different species. A large amount of literature shows that the lack of miR-125 can cause abnormal development of the cardiovascular system in the embryonic period. At the same time, the miR-125 family participates in the occurrence and development of a variety of cardiovascular and cerebrovascular diseases, including myocardial ischemia, atherosclerosis, ischemia-reperfusion injury, ischemic stroke, and heart failure directly or indirectly. In this article, we summarized the role of the miR-125 family in the development and maturation of cardiovascular system, the occurrence and development of cardiovascular and cerebrovascular diseases, and its important value in the current fiery stem cell therapy. In addition, we presented this in the form of table and diagrams. We also discussed the difficulties and challenges faced by the miR-125 family in clinical applications.

Neural stem cell delivery using brain-derived tissue-specific bioink for recovering from traumatic brain injury

Traumatic brain injury is one of the leading causes of accidental death and disability. The loss of parts in a severely injured brain induces edema, neuronal apoptosis, and neuroinflammation. Recently, stem cell transplantation demonstrated regenerative efficacy in an injured brain. However, the efficacy of current stem cell therapy needs improvement to resolve issues such as low survival of implanted stem cells and low efficacy of differentiation into respective cells. We developed brain-derived decellularized extracellular matrix (BdECM) bioink that is printable and has native brain-like stiffness. This study aimed to fabricate injured cavity-fit scaffold with BdECM bioink and assessed the utility of BdECM bioink for stem cell delivery to a traumatically injured brain. Our BdECM bioink had shear thinning property for three-dimensional (3D)-cell-printing and physical properties and fiber structures comparable to those of the native brain, which is important for tissue integration after implantation. The human neural stem cells (NSCs) (F3 cells) laden with BdECM bioink were found to be fully differentiated to neurons; the levels of markers for mature differentiated neurons were higher than those observed with collagen bioink in vitro. Moreover, the BdECM bioink demonstrated potential in defect-fit carrier fabrication with 3D cell-printing, based on the rheological properties and shape fidelity of the material. As F3 cell-laden BdECM bioink was transplanted into the motor cortex of a rat brain, high efficacy of differentiation into mature neurons was observed in the transplanted NSCs; notably increased level of MAP2, a marker of neuronal differentiation, was observed. Furthermore, the transplanted-cell bioink suppressed reactive astrogliosis and microglial activation that may impede regeneration of the injured brain. The brain-specific material reported here is favorable for NSC differentiation and suppression of neuroinflammation and is expected to successfully support regeneration of a traumatically injured brain.

Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies.

ABSTRACTBronchopulmonary dysplasia (BPD) is a chronic lung disease caused by exposure to high levels of oxygen (hyperoxia) and is the most common complication that affects preterm newborns. At present, there is no cure for BPD. Infants can recover from BPD; however, they will suffer from significant morbidity into adulthood in the form of neurodevelopmental impairment, asthma and emphysematous changes of the lung. The development of hyperoxia-induced lung injury models in small and large animals to test potential treatments for BPD has shown some success, yet a lack of standardization in approaches and methods makes clinical translation difficult. In vitro models have also been developed to investigate the molecular pathways altered during BPD and to address the pitfalls associated with animal models. Preclinical studies have investigated the efficacy of stem cell-based therapies to improve lung morphology after damage. However, variability regarding the type of animal model and duration of hyperoxia to elicit damage exists in the literature. These models should be further developed and standardized, to cover the degree and duration of hyperoxia, type of animal model, and lung injury endpoint, to improve their translational relevance. The purpose of this Review is to highlight concerns associated with current animal models of hyperoxia-induced BPD and to show the potential of in vitro models to complement in vivo studies in the significant improvement to our understanding of BPD pathogenesis and treatment. The status of current stem cell therapies for treatment of BPD is also discussed. We offer suggestions to optimize models and therapeutic modalities for treatment of hyperoxia-induced lung damage in order to advance the standardization of procedures for clinical translation.

Induction of Differentiation of Mesenchymal Stem Cells into Retinal Pigment Epithelial Cells for Retinal Regeneration by Using Ciliary Neurotrophic Factor in Diabetic Rats.

Diabetic retinopathy (DR) is a common cause of blindness all over the world. Bone marrow mesenchymal stem cells (BMSCs) have been considered as a promising strategy for retinal regeneration in the treatment of DR. However, the poor viability and low levels of BMSCs engraftment limit the therapeutic potential of BMSCs. The present study aimed to examine the direct induction of BMSCs differentiation into the cell types related to retinal regeneration by using soluble cytokine ciliary neurotrophic factor (CNTF). We observed remarkably increased expression of cellular retinaldehyde-binding protein (CRALBP) and retinoid isomerohydrolase (RPE65) in BMSCs treated with CNTF in vitro, indicating the directional differentiation of BMSCs into the retinal pigment epithelium (RPE) cells, which are crucial for retinal healing. In vivo, the diabetic rat model was established by use of streptozotocin (STZ), and animals treated with BMSCs+CNTF exhibited better viability and higher delivery efficiency of the transplanted cells than those treated with BMSCs injection alone. Similar to the in-vitro result, treatment with BMSCs and CNTF combined led to the differentiation of BMSCs into beneficial cells (RPE cells), and accelerated retinal healing characterized by the activation of rod photoreceptor cells and phagocytosis function of RPE cells. In conclusion, CNTF contributes to the differentiation of BMSCs into RPE cells, which may help overcome the current stem cell therapy limitations in the field of retinal regeneration.

Therapeutic Application of Chick Early Amniotic Fluid: Effective Rescue of Acute Myocardial Ischemic Injury by Intravenous Administration

Background: Stem cell therapy has been reported to be effective and promising for the treatment of adult myocardial ischemic injury. However, few stem cells survive and differentiate into cardiomyocytes after transplantation and the mechanisms of repair by stem cells are multiplex and undetermined. Furthermore, different types of stem cells elicit various degrees of immunogenicity and tumorigenicity, which poses a high risk for their future clinical applications. Chick early amniotic fluid (ceAF) administration could be a valuable alternative or addition to current stem cell therapy. Methods: Mice myocardial infarction and swine ischemic reperfusion injury models were established and received ceAF by intravenous injection after surgery. Findings: ceAF efficiently rescued damaged cardiac tissue, stimulated cardiac repair, and markedly improved heart function in adult mice and swine models of myocardial ischemic injury. Notably, no noticeable abnormalities were observed in the treated animals and no systemic inflammation or immune reactions were perceived after recurring intravenous infusion of ceAF in rats and monkeys. We further show that ceAF promoted heart repair through multiple mechanisms, including, down-regulation of the Hippo-YAP signaling pathway, increased cell proliferation, improved angiogenesis, and recruitment of pro-healing macrophages after myocardial damage in adult mice and pigs. Interpretation: Together, our data indicate that intravenous injection of ceAF effectively rescued ischemic heart injury through multiplex mechanisms and could be a novel and safe non-invasive therapy for ischemic heart disease in substitution of stem cell therapy. Funding Information: This work was supported by ZheJiang HygeianCells Biomedical Co. Ltd, Hangzhou, Zhejiang, 310019, China. Declaration of Interests: None declared. Ethics Approval Statement: All animal protocols were reviewed and approved by the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, Publication No. 85-23, Revised), by the U.S. Department of Agriculture (USDA) in the Animal Welfare Act (Public Law 99-198), and were carried out under the supervision of the Fudan University Institutional Animal Care and Use Committee (IACUC), Shanghai Mincal Medical Research Co. IACUC, WuXi AppTec (Shanghai, China) IACUC, or the JOINN Laboratories IACUC (Suzhou, China).

Management of refractory angina: an update.

Despite the use of anti-anginal drugs and/or percutaneous coronary interventions (PCI) or coronary artery bypass grafting, the proportion of patients with coronary artery disease who have daily or weekly angina ranges from 2% to 24%. Refractory angina refers to long-lasting symptoms (for >3 months) due to established reversible ischaemia, which cannot be controlled by escalating medical therapy with the use of 2nd- and 3rd-line pharmacological agents, bypass grafting, or stenting. While there is uncertain prognostic benefit, the treatment of refractory angina is important to improve the quality of life of the patients affected. This review focuses on conventional pharmacological approaches to treating refractory angina, including guideline directed drug combination and dosages. The symptomatic and prognostic impact of advanced and novel revascularization strategies such as chronic total occlusion PCI, transmyocardial laser revascularization, coronary sinus occlusion, radiation therapy for recurrent restenosis, and spinal cord stimulation are also covered and recommendations of the 2019 ESC Guidelines on the Diagnosis and Management of Chronic Coronary Syndromes discussed. Finally, the potential clinical use of current angiogenetic and stem cell therapies in reducing ischaemia and/or pain is evaluated.

Stem Cells in Rotator Cuff Injuries and Reconstructions: A Systematic Review and Meta-Analysis

Current Stem Cell Research & Therapy, 2019, 14(8): 683-697 Heyong Yin's affiliation should be: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing China; Zexing Yan's affiliation should be: Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, No.324, Road Jing Wu Wei Qi, Jinan 250021, Shandong, China. The Original Paragraph Provided is Mentioned Below: Fanxiao Liu1, Qingqi Meng2, Heyong Yin3,* and Zexing Yan3,* 1Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, No.324, Road Jing Wu Wei Qi, Jinan 250021, Shandong, China; 3Department of Trauma Surgery, University of Regensburg, Am biopark 9, 93049 Regensburg, Germany.

Intramyocardial Transplantation of MSC-Loading Injectable Hydrogels after Myocardial Infarction in a Murine Model

One of the major issues facing current cardiac stem cell therapies for preventing postinfarct heart failure is the low retention and survival rates of transplanted cells within the injured myocardium, limiting their therapeutic efficacy. Recently, the use of scaffolding biomaterials has gained attention for improving and maximizing stem cell therapy. The objective of this protocol is to introduce a simple and straightforward technique to transplant bone marrow-derived mesenchymal stem cells (MSCs) using injectable hydroxyphenyl propionic acid (GH) hydrogels; the hydrogels are favorable as a cell delivery platform for cardiac tissue engineering applications due to their ability to be cross-linked in situ and high biocompatibility. We present a simple method to fabricate MSC-loading GH hydrogels (MSC/hydrogels) and evaluate their survival and proliferation in three-dimensional (3D) in vitro culture. In addition, we demonstrate a technique for intramyocardial transplantation of MSC/hydrogels in mice, describing a surgical procedure to induce myocardial infarction (MI) via left anterior descending (LAD) coronary artery ligation and subsequent MSC/hydrogels transplantation.

Multifaceted application of nanoparticle-based labeling strategies for stem cell therapy

Stem cell therapy can overcome many unmet clinical challenges that have proven intractable with traditional medicine and treatment strategies because of their strong ability to recover and regenerate injured tissue. Nanoparticle-based labeling agents, in combination with current imaging technologies, have been used to monitor the location, migration, survival, and differentiation of transplanted stem cells in therapeutic processes to fully understand their fates in vivo. In addition, various kinds of functional nanoparticles can exert unique biological effects on stem cells to overcome some problems of current stem cell therapy involving cell homing, survival, retention, and directional differentiation. Moreover, nanoparticle-based theranostic labeling, in which both imaging and treatment modalities are delivered with the stem cells, has emerged as a new strategy to enhance the therapeutic effect of stem cells and shows great potential for future stem cell therapy. The aim of this review is to describe the current roles played by nanoparticles in cell tracking, cell fate regulation, and theranostic labeling in stem cell therapy. Important issues and perspectives on the potential growth of this area are also critically discussed.

4D Self-Morphing Culture Substrate for Modulating Cell Differentiation.

As the most versatile and promising cell source, stem cells have been studied in regenerative medicine for two decades. Currently available culturing techniques utilize a 2D or 3D microenvironment for supporting the growth and proliferation of stem cells. However, these culture systems fail to fully reflect the supportive biological environment in which stem cells reside in vivo, which contain dynamic biophysical growth cues. Herein, a 4D programmable culture substrate with a self‐morphing capability is presented as a means to enhance dynamic cell growth and induce differentiation of stem cells. To function as a model system, a 4D neural culture substrate is fabricated using a combination of printing and imprinting techniques keyed to the different biological features of neural stem cells (NSCs) at different differentiation stages. Results show the 4D culture substrate demonstrates a time‐dependent self‐morphing process that plays an essential role in regulating NSC behaviors in a spatiotemporal manner and enhances neural differentiation of NSCs along with significant axonal alignment. This study of a customized, dynamic substrate revolutionizes current stem cell therapies, and can further have a far‐reaching impact on improving tissue regeneration and mimicking specific disease progression, as well as other impacts on materials and life science research.

Induction of Cardiomyogenesis in Stem Cells Isolated from Human Exfoliated Deciduous Teeth

Background: The natural transition from neonatal deciduous teeth to adult permanent teeth is a physiological phenomenon. Miura et al. reported the isolation and characterization of stem cells from the pulp of human exfoliated deciduous teeth (SHED). The great majority of current stem cell therapies use human adult stem cells. Since adult stem cells are multi-potent. SHED have demonstrated to have the capability to differentiate into osteogenic and odontogenic cells, adipocytes, and neural cells. When transplanted in immunocompromised mice, SHED were able to form bone. In addition, SHED have been able to differentiate into functional odontoblast and angiogenic endothelial cells. Aims and Objective: There are two objectives in our study; First, we want to confirm that SHED cells differentiate into osteogenic and neurotic cells. Second, we shall also examine whether SHED stem cells can also differentiate into cardiomyocytes. Material and Method: SHED stem cells are subjected to cardiomyogenic, neurogenic, and osteogenic induction treatment. The treated cells are the subjected to real time PCR and mmuno-histochemical analysis. The presence of calcium deposits with Alizarin Red S staining for SHED cells treated with osteogenic media was used to confirm osteogenic differentiation. Results: Our study confirmed that SHED cells differentiate into osteogenic and neurotic cells. For the first time we showed that SHED cells can also differentiate into cardiomyocytes. Conclusion: Due to their potentials and its neural crest origin, SHED are an ideal stem cell source for tissue regeneration.