Current stem cell research & therapy最新文献

Adipose-derived stem cells (ADSCs) have been described as one of the most potent and accessible human adult stem cells which can be utilized in various therapeutic approaches. Due to the wide variety of cytokines and GFs secreted by them, ADSCs can be used for controlled drug release. These cells can be used for proliferation and differentiation of tissues regardless of survival conditions and immunologic problems. Because of their ability to differentiate into various lineages, ADSCs can be used in musculoskeletal problems, diabetes, heart diseases, obesity, neurologic and nephrogenic diseases, and wound healing, as well as applications in regenerative medicine such as osteogenic, cartilage, tendon, muscle, skin, CNS, cardiac and vascularization, as well as liver and even periodontal regeneration. To maintain the highest viability and efficiency, companies that provide ADSCs should offer the best product quality to gain market share and scientists need to acquire an understanding of sources where they can find the best products available. Therefore, in this article, we have reviewed the available products, companies and the market size currently available for ADSCs. Enormous effort has been made to list the most important trials, products and companies currently existent in the field. To achieve better outcomes in scientific research, there is the need to compare the products available and choose the best option according to desired goals. Thus, this paper provides a valuable reference for those interested in the field of ADSCs and their applications.

Under a variety of physical and experimental settings, stem cells are able to self-renew and differentiate into specialized adult cells. MSCs (mesenchymal stromal/stem cells) are multipotent stem cells present in a wide range of fetal, embryonic, and adult tissues. They are the progenitors of a variety of specialized cells and are considered crucial tools in tissue engineering. MSCs, derived from various tissues, including cord blood, placenta, bone marrow, and dental tissues, have been extensively examined in tissue repair, immune modulation, etc. Increasing the vitality of MSCs and restoring cellular mechanisms are important factors in treatment success. Oxidative stress harms cellular molecules such as DNA, proteins, and lipids due to the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cells and tissues or insufficiency of antioxidant systems that can inactivate them. Oxidative stress has a close link with inflammation as a pathophysiological process. ROS can mediate the expression of proinflammatory genes via intracellular signaling pathways and initiate the chronic inflammatory state. At the same time, inflammatory cells secrete a large number of reactive species that cause increased oxidative stress at sites of inflammation. In inflammatory diseases, the differentiation of stem cells and the regenerative and wound healing process can be affected differently by the increase of oxidative stress. Recent studies have indicated that dental pulp stem cells (DPSCs), as a resource of adult stem cells, are an attractive option for cell therapy in diseases such as neurological diseases, diabetes, cardiological diseases, etc., as well as its treatment potential in pulp inflammation. The future of oxidative stressinflammation cycle and/or ageing therapies involves the selective elimination of senescent cells, also known as senolysis, which prevents various age-related diseases. Most pathologies are implicated on the effects of ageing without exerting undesirable side effects.

The intervertebral discs (IVDs) are a relatively mobile joint that interconnects vertebrae of the spine. Intervertebral disc degeneration (IVDD) is one of the leading causes of low back pain, which is most often related to patient morbidity as well as high medical costs. Patients with chronic IVDD often need surgery that may sometimes lead to biomechanical complications as well as augmented degeneration of the adjacent segments. Moreover, treatment modalities like rigid intervertebral fusion, dynamic instrumentation, as well as other surgical interventions are still controversial. Mesenchymal stem cells (MSCs) have exhibited to have immunomodulatory functions and the ability to differentiate into cartilage, making these cells possibly an epitome for IVD regeneration. Transplanted MSCs were able to repair IVDD back to the normal disc milieu via the activation of the generation of extracellular matrix (ECM) proteins such as aggrecan, proteoglycans and collagen types I and II. IVD milieu clues like, periostin, cluster of differentiation, tumor necrosis factor alpha, interleukins, chemokines, transforming growth factor beta, reactive oxygen species, toll-like receptors, tyrosine protein kinase receptor and disialoganglioside, exosomes are capable of influencing the MSCs during treatment of IVDD. ECM microenvironment clues above have potentials as biomarkers as well as accurate molecular targets for therapeutic intervention in IVDD.

Tumor recurrence is a colossal challenge in clinical oncology. This multifactorial problem is attributed to the emergence of additional genetic mutations and the presence of dormant cancer cells. However, the plasticity of non-stem cancer cells and the acquisition of cancer stem cell (CSC) functionality is another contributing factor to tumor recurrence. Herein, I focus attention on the mechanisms that fuel cancer cell de-differentiation and the interplay between intra-cellular regulators and tumor microenvironment (TME) landscape that promotes cancer cell stemness. Our understanding of the mechanisms underlying tumor cell de-differentiation is crucial for developing innovative therapeutic strategies that prevent cancer from ever recurring.

Background: Increased oxygen species levels can induce mitochondrial DNA damage and chromosomal aberrations and cause defective stem cell differentiation, leading finally to senescence of stem cells. In recent years, several studies have reported that antioxidants can improve stem cell survival and subsequently affect the potency and differentiation of these cells. Finding factors, which reduce the senescence tendency of stem cells upon expansion, has great potential for cellular therapy in regenerative medicine. This study aimed to evaluate the effects of L-carnitine (LC) on the aging of C-kit+ hematopoietic progenitor cells (HPCs) via examining the expression of some signaling pathway components.

Methods: For this purpose, bone marrow resident C-kit+ HPCs were enriched by the magnetic-activated cell sorting (MACS) method and were characterized using flow cytometry as well as immunocytochemistry. Cells were treated with LC, and at the end of the treatment period, the cells were subjected to the realtime PCR technique along with a western blotting assay for measurement of the telomere length and assessment of protein expression, respectively.

Results: The results showed that 0.2 mM LC caused the elongation of the telomere length and increased the TERT protein expression. In addition, a significant increase was observed in the protein expression of p38, p53, BCL2, and p16 as key components of the telomere-dependent pathway.

Conclusion: It can be concluded that LC can increase the telomere length as an effective factor in increasing the cell survival and maintenance of the C-kit+ HPCs via these signaling pathway components.

Background: Human pluripotent stem cell (hPSC)-derived kidney organoids may contribute to disease modeling and the generation of kidney replacement tissues. However, the realization of such applications requires the induction of hPSCs into functional mature organoids. One of the key questions for this process is whether a specific vascular system exists for nephrogenesis. Our previous study showed that short-term (2 weeks) implantation of hPSC-derived organoids below the kidney capsules of unilaterally nephrectomized and immunodeficient mice resulted in the enlargement of organoids and production of vascular cells, although signs of maturation were lacking.

Methods: Organoids were induced for 15 days in vitro and then grafted below kidney capsules of the same unilaterally nephrectomized immunodeficient mouse model to examine whether medium-term (4 weeks) implantation could improve organoid maturation and vascularization, as evaluated by immunofluorescence and transmission electron microscopy.

Results: We demonstrated that after 2-4 weeks of implantation, renal organoids formed host-derived vascularization and matured without any exogenous vascular endothelial growth factor. Glomerular filtration barrier maturation was evidenced by glomerular basement membrane deposition, perforated glomerular endothelial cell development, and apical, basal podocyte polarization. A polarized monolayer epithelium and extensive brush border were also observed for tubular epithelial cells.

Conclusions: Our results indicate that the in vivo microenvironment is important for the maturation of human kidney organoids. Stromal expansion and a reduction of nephron structures were observed following longer-term (12 weeks) implantation, suggesting effects on off-target cells during the induction process. Accordingly, induction efficiency and transplantation models should be improved in the future.

The introduction of an experimental animal model for myocardial infarction (MI) has particular importance. Research done on large animals provides valuable information for the researchers because of the similar characteristics of their hearts compared to humans, but the cost of purchasing and maintaining them is high. In comparison, using small animals has advantages, such as they are easy to work with and have low purchase and maintenance costs. However, in some of these animals, due to less similarity of the heart to humans, they cannot simulate the natural pathogenesis of human MI. Moreover, there are different methods for the induction of MI in animals; each has its own advantages and disadvantages. However, a method must be chosen to simulate the natural pathogenesis of MI with minimal complication. Currently, attempts are being made for myocardial regeneration after MI using the direct transplantation of stem cells or an engineered scaffold. The scaffold creates a 3D ambiance for the cultured cells. The task of tissue engineering is to optimize the scaffold with appropriate systems for the separation, proliferation, and differentiation of the desired cells until they are capable of promoting the threedimensional and appropriate growth of the tissue. The purpose of tissue engineering in cardiac is the use of scaffolds and cells in the damaged area, followed by the improvement of the heart function through automatic pulsation, communication with the host vessels, and electrical coupling with the myocardium, eventually creating a force to increase the heart function.

Resistance to chemotherapy poses a major challenge for cancer treatment. Reactivating a stem cell program resembling that seen in embryonic development can lead cancer cells to acquire a stem-cell phenotype characterized by expression of stemness genes, pluripotency, high self-renewal ability, and tumor-initiating capability. These cancer stem cells (CSCs) are usually resistant to anticancer drugs and are likely involved in treatment failure in many cancer types. Ewing sarcoma (ES) is a pediatric cancer type typically resulting from a typical genetic alteration affecting bone or soft tissues. Despite advances in treatment, survival prognostic remains poor for patients with refractory or recurrent disease. Here, we review the increasing evidence indicating that ES tumors contain a CSC subpopulation expressing stem cell genes, including BM1, OCT3/4, NANOG, and SOX2, that plays a role in resistance to drug treatment, and current experimental strategies that successfully counteract chemoresistance mediated by CSCs in ES.

Background: Though adipose-derived stem cells (ADSCs) have potential applications for the repair and regeneration of damaged tissues, limited studies have defined the function of ADSCs on dermal fibroblasts. Our RNA-seq sequencing identified differentially expressed SOCS3 in frostbite injury.

Objective: In the current study, we aim to examine the hypothesis that extracellular vesicles derived from adipose-derived mesenchymal stem cells (ADSCs-EVs) may modulate SOCS3/TGF-β1 signaling in wound healing of frostbite injury.

Methods: sh-SOCS3 and sh-TGF-β1 were introduced to explore the biological role of SOCS3 in frostbite injury by detecting the proliferation and migration of human skin fibroblast (HSF) cells and the wound healing in mice. Furthermore, the extracted ADSCs-EVs were interfered with HSF cells in vitro or injected into the frostbitten mouse model in vivo.

Results: Upregulation of SOCS3 occurred in the skin tissues of frostbitten mice. Compared to sh-NC, the wound healing rate of sh-SOCS3 presented higher on day 7(31.34±4.35 vs 41.83±3.74, p < 0.05) and day 14 (63.42±6.01 vs 88.99±5.12, p < 0.05) after injury. Silencing SOCS3 can promote frostbite wound healing. Moreover, SOCS3 downregulated TGF-β1 to suppress the proliferation and migration of HSF cells, thus impeding the skin wound healing. Additionally, ADSCs-EVs could enhance the proliferation and migration of HSF cells according to the results of CCK-8 assay (p < 0.05), scratch test (17.82±4.25 vs 49.78±2.54, p < 0.05) and Transwell assay (42.33±6.81 vs 91.33±7.02, p < 0.05), and regulate the expression of SOCS3/TGF-β1. The role of ADSCs-EVs in frostbite wound healing was also confirmed in vivo. ADSCs-EVs could promote frostbite wound healing by downregulating the expression of SOCS3 and upregulating the expression of TGF-β1 and collagen I.

Conclusion: Collectively, ADSCs-EVs inhibit SOCS3 and facilitate the expression of TGF-β1, which promotes the proliferation and migration of HSF cells and subsequently enhances wound healing of frostbite injury.

Background: Mesenchymal stem cells (MSCs) are partially differentiated multipotent cells. They can be derived from various tissues such as the umbilical cord, bone marrow, and adipose tissue. Intrathecal administration of MSCs has shown efficacy for various neurological conditions including multiple sclerosis, autism, traumatic brain injury, and many more.

Objective: This review will seek to determine whether there are any serious adverse events associated with spinal intrathecal administration of MSCs.

Methods: PubMed was used to search the scientific literature for serious adverse events that are related to spinal intrathecal administration of MSCs. Disease specific searches were performed for neurological conditions that could benefit from intrathecal administration of MSCs. In addition, a general serious adverse events search was performed to identify any additional adverse events.

Results and discussion: A total of 39 studies were included in our analysis. None of the studies reported serious adverse events related to spinal intrathecal administration of MSCs. Notably, no infections, clinical rejection, or tumors were identified.

Conclusion: Properly performed spinal intrathecal injection of MSCs is exceedingly safe, with no serious adverse events reported based on our exhaustive literature search.