Up to now, the gingiva-derived mesenchymal stem cells (GMSCs) as a new postnatal stem cells have been isolated and characterized with multipotential differentiation capabilities in vitro. However, ...the in vivo efficacy of utilizing the GMSCs in bone regeneration remains obscure. First of all, we identified canonical MSCs in human gingival tissue, which possessed homogenous immunophenotype (CD34(-)CD45(-)CD29(+)CD105(+)CD90(+) STRO-1(+)) and had tri-lineage differentiation potential (osteoblasts, adipocytes, and chondrocytes). Next, we examined the efficacy of utilizing these stem cells in bone tissue regeneration; the enhanced green fluorescent protein-labeled GMSCs seeded on type I collagen gel were implanted into the mandibular defects as well as the critical-sized calvarial defects in Sprague Dawley rats. We first demonstrated that GMSCs could repair the mandibular wounds and calvarial defects at 2 months in rats postsurgical reconstruction. Histomorphological analysis and image of fluorescence microscope certified that new bone in the defect areas was derived from the transplanted GMSCs. Immunohistochemical analysis of green fluorescent protein, human collagen I, and osteopontin further confirmed our conclusion. The above results implied that mesenchymal stem cells derived from gingival tissue could be a novel source for stem cell-based therapy in bone reconstruction in clinical applications.
Diabetic wounds are a worldwide health problem, with increasing morbidity and risk of amputation. This study investigated a novel application of a human decellularized adipose tissue matrix (hDAM) as ...a natural 3D scaffold for delivering human adipose-derived stem cells (hASCs) to diabetic wounds. The porous structure, ability to preserve extracellular matrix components, and convenient storage conditions of decellularized hDAM make it a potential clinical wound dressing material. The hASCs cultured in the hDAM scaffold exhibited a fibroblast-like morphology and more evenly distributed cells on both the surface and inside the porous structure of the hDAM scaffold. In addition, the biocompatibility of hDAM enhanced the hASCs proliferation, maintenance of the stemness properties, and release of angiogenic cytokines compared to those under standard culture conditions. Moreover, cell suspensions derived from hASCs cultured in hDAM scaffolds promoted the proliferation and migration of human umbilical vascular endothelial cells, indicating its potential effect in promoting angiogenesis. Furthermore, the potential clinical therapeutic efficacy of the hASC-hDAM composite for diabetic wound healing was evaluated using a full-thickness wound model in diabetic mice. Diabetic rats treated with the hASCs-seeded hDAM scaffold displayed enhanced wound healing efficiency, including an improved blood perfusion volume for wounds, reduced number of inflammatory cells, and enhanced epithelization. This study demonstrated that the 3D model that combined hASCs and an hDAM could accelerate wound healing and might hold potential for clinical application to enhance diabetic wound healing and regeneration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is an urgent medical need to develop effective therapies that can ameliorate damage to the radiation-exposed hematopoietic system. Nanozymes with robust antioxidant properties have a ...therapeutic potential for mitigating radiation-induced hematopoietic injury. However, enhancing nanozyme recruitment to injured tissues in vivo while maintaining their catalytic activity remains a great challenge. Herein, we present the design and preparation of a biomimetic nanoparticle, a mesenchymal stem cell membrane camouflaged Prussian blue nanozyme (PB@MSCM), which exhibits biocompatible surface properties and demonstrates enhanced injury site-targeting towards the irradiated murine bone marrow niche. Notably, the constructed PB@MSCM possessed redox enzyme-mimic catalytic activity and could scavenge overproduced reactive oxygen species in the irradiated bone marrow cells, both in vitro and ex vivo. More importantly, the administration of PB@MSCM significantly mitigated hematopoietic cell apoptosis and accelerated the regeneration of hematopoietic stem and progenitor cells. Our findings provide a new targeted strategy to improve nanozyme therapy in vivo and mitigate radiation-induced hematopoietic injury.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•We successfully produced a thermal sensitive hDAT-gel.•The hDAT-gel supports hASCs culture in vitro.•The hDAT-gel containing hASCs has wound healing efficacy.
Acellular matrix ...hydrogels have been extracted from a variety of tissues currently, which have been widely exploited for various applications. What is more, hydrogels derived from porcine myocardium matrix have entered clinical trials (NCT02305602) for the prevention and treatment of heart failure post-myocardial infarction. However, few scholars have analyzed the adipose acellular matrix hydrogels. Here we report an injectable hydrogel entirely from human decellularized adipose tissue (hDAT-gel) and explore the innovative application in wound healing combining with human adipose-derived stem cells (hASCs). We postulated that hDAT-gel could provide hASCs with a 3D vivo-like ecological niche necessary to enhance stem cell engraftment, survival as well as differentiation to improve the quality of wound healing. Consequently, a temperature-responsive hDAT-gel was successfully produced, which could undergo sol-gel transition at 37℃. In vitro, hASCs could survive and proliferate well in the self-assembled gel which retained important protein components. In vivo, when the hASCs-embedded hDAT-gels were injected into the full-thickness cutaneous wound of mice, the wound healed rapidly through obvious neovascularization especially within 7 days. Our study demonstrated that the hDAT-gel containing hASCs could accelerate the vascularization of the wound site and speed up the wound healing to some extent. It is a promising injectable biomaterial for stem cell delivery and wound repair.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To investigate an important role of the stem cells in reconstructing the tissues and organs.
Based on our own researches and combined with the review of the literature at home and abroad, the latest ...development of the cell therapy with the stem cells and the application of the seed cells in the tissue engineering were analyzed.
As the stem cells are the origin of the human tissues and organs and have a higher self-renewal ability and extensive characteristics of proliferation in vitro, their imbedding and multi-differential potentialities were illustrated. Both the embryonic stem cells and the adult stem cells had a wide prospect as ideal seed cells for reparation and reconstruction of the impaired human tissues and organs.
The stem cells can play an important role in repairing and reconstructing the injured tissues and organs and they have a promising prospect in clinical application. The further research and wide application of the stems cells will significantly improve the therapeutic effects on the injure
The major obstacle for applications of human induced pluripotent stem cells (hiPSCs) is efficient and controlled lineage-specific differentiation. Hence, a deeper understanding of the initial ...populations of hiPSCs is required to instruct proficient lineage commitment.
hiPSCs were generated from somatic cells by transduction of 4 human transcription factors (OCT4, SOX2, KLF4, and C-MYC) using Sendai virus vectors. Genome-wide DNA methylation analysis and transcriptional analysis were performed to evaluate the pluripotent capacity and somatic memory state of hiPSCs. Flow cytometric analysis and colony assays were performed to assess the hematopoietic differentiation capacity of hiPSCs.
Here, we reveal human umbilical arterial endothelial cell-derived induced pluripotent stem cells (HuA-iPSCs) exhibit indistinguishable pluripotency in comparison with human embryonic stem cells and hiPSCs derived from other tissues of origin (umbilical vein endothelial cells, cord blood, foreskin fibroblasts, and fetal skin fibroblasts). However, HuA-iPSCs retain a transcriptional memory typical of the parental human umbilical cord arterial endothelial cells, together with a strikingly similar DNA methylation signature to umbilical cord blood-derived induced pluripotent stem cells that distinguishes them from other human pluripotent stem cells. Ultimately, HuA-iPSCs are most efficient in targeted differentiation toward hematopoietic lineage among all human pluripotent stem cells based on the functional and quantitative evaluation of both flow cytometric analysis and colony assays. Application of the Rho-kinase activator significantly reduces the effects of preferential hematopoietic differentiation in HuA-iPSCs, reflected in CD34
cell percentage of day 7, hematopoietic/endothelial-associated gene expression, and even colony-forming unit numbers.
Collectively, our data suggest that somatic cell memory may predispose HuA-iPSCs to differentiate more amenably into hematopoietic fate, bringing us closer to generating hematopoietic cell types in vitro from nonhematopoietic tissue for therapeutic applications.
Mesenchymal stem cells (MSCs) have shown potential for the repair of defective tissues and peripheral nerve injuries. However, local treatment alone may lead to cell loss, low viability, and ...diminished paracrine action owing to the lack of effective biological scaffolds. To improve the therapeutic effects of MSCs, bioactive scaffolds that mimic the stem cell microenvironment in vivo should be constructed. We developed an injectable decellularised matrix hydrogel (DAM-gel) to simulate the stem cell microenvironment using combined physical, chemical, and enzymatic digestions of human adipose tissues. The DAM-gel was loaded with rat adipose-derived mesenchymal stem cells (ADSCs) to repair sciatic nerve defects. Compared with ADSCs alone, the ADSC-loaded DAM-gel promoted the proliferation of Schwann cells in vitro, which are important in sciatic nerve regeneration. Chitin biological conduits filled with ADSC-DAM-gel composites were designed to bridge the sciatic nerve defects. Axonal regeneration and the recovery of neurological function in the ADSC-DAM-gel group increased post-surgery compared with the control group (blank conduit, ADSCs, and DAM-gel group), as confirmed by a CatWalk gait analysis, electrophysiology, and nerve/muscle histology. The ADSC-loaded DAM-gel-treated rats retained the improved peripheral nerve regeneration. Therefore, DAM-gels have great potential for enhancing the repair capacity of ADSCs in peripheral nerve defects.
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•Fabricated DAM-gel is a thermosensitive material with a loose network structure.•It has strong biocompatibility and rheological properties, ideal for NGC filling.•In vitro co-culture of DAM-gel-loaded ADSCs increased SC proliferative activity.•In vivo transplantation of DAM-gel-loaded ADSCs promotes axonal regeneration.•It promotes recovery of motor function after 10 mm sciatic nerve injury in rats.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To study the expression of tumorigenesis-related stem cell markers Lgr5 and CD44 in different pathological types of intestinal polyps and their clinical significance in predicting tumorigenesis.
A ...total of 145 cases of colorectal polyps, adenomas and cancer tissues were obtained by colonoscopy biopsy. Immunohistochemistry was employed to detect the expression of Lgr5 and CD44 to analyze their relationship with the occurrence and prognosis of colon and rectal cancer.
The expression of CD44 in colon cancer tissue was 95.65%, significantly higher than that in normal mucosa (5%), inflammatory hyperplastic polyps (22.58%), tubular adenomatous polyps (55.26%) and villous polyps (75.76%) (P<0.05). The expression of Lgr5 in colorectal cancer was up to 95.65% while negative in normal colorectal tissue and was 16.12% in inflammatory hyperplastic tissues (P<0.05). The expression rate of Lgr5 was 86.84% in tubular adenoma and 93.94% in villous polyps, both comparable with that in colon cancer (P>0.05). Correlation analys
Reprogramming somatic cells into megakaryocytes (MKs) would provide a promising source of platelets. However, using a pharmacological approach to generate human MKs from somatic cells remains an ...unmet challenge. Here, we report that a combination of four small molecules (4M) successfully converted human cord blood erythroblasts (EBs) into induced MKs (iMKs). The iMKs could produce proplatelets and release functional platelets, functionally resembling natural MKs. Reprogramming trajectory analysis revealed an efficient cell fate conversion of EBs into iMKs by 4M via the intermediate state of bipotent precursors. 4M induced chromatin remodeling and drove the transition of transcription factor (TF) regulatory network from key erythroid TFs to essential TFs for megakaryopoiesis, including FLI1 and MEIS1. These results demonstrate that the chemical reprogramming of cord blood EBs into iMKs provides a simple and efficient approach to generate MKs and platelets for clinical applications.
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•A small-molecule cocktail (4M) converts human cord blood erythroblasts into iMKs•The iMKs resemble natural MKs and give rise to functional platelets•ScRNA-seq reveals conversion of EBs into two types of iMKs via an iPEM intermediate•4M induces changes in chromatin accessibility dynamics and opens MK-related loci
A small-molecule cocktail reprograms human cord blood erythroblasts into induced megakaryocytes with ex vivo functionality. The four small molecules extensively remodel the chromatin and induce the dynamic network transition from erythroid master genes to FLI1 and other megakaryopoiesis-related genes via a bi-potent precursor state.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
