Migration Of Mesenchymal Stem Cells Research Articles

Sodium alginate hydrogel integrated with type III collagen and mesenchymal stem cell to promote endometrium regeneration and fertility restoration

A thinner endometrium has been linked to implantation failure, and various therapeutic strategies have been attempted to improve endometrial regeneration, including the use of mesenchymal stem cells (MSCs). However, low survival and retention rates of transplanted stem cells are main obstacles to efficient stem cell therapy in thin endometrium. Collagen type III is a key component of the extracellular matrix, plays a crucial role in promoting cell proliferation and differentiation, and has been identified as the major collagen expressed at the implantation site. Herein, composite alginate hydrogel containing recombinant type III collagen (rCo III) and umbilical cord mesenchymal stem cells are developed. rCo III serves as favorable bioactive molecule, displaying that rCo III administration promotes MSCs proliferation, stemness maintenance and migration. Moreover, rCo III administration enhances cell viability and migration of mouse endometrial stromal cells (ESCs). In a mouse model of thin endometrium, the Alg-rCo III hydrogel loaded with MSCs (MSC/Alg-rCo III) significantly induces endometrial regeneration and fertility enhancement in vivo. Further studies demonstrate that the MSC/Alg-rCo III hydrogel promoted endometrial function recovery partly by regulating mesenchymal-epithelial transition of ESCs. Taken together, the combination of Alg-rCo III hydrogel and MSCs has shown promising results in promoting endometrium regeneration and fertility restoration, and may provide new therapeutic options for endometrial disease.

Decellularized allogeneic cartilage paste with human costal cartilage and crosslinked hyaluronic acid-carboxymethyl cellulose carrier augments microfracture for improved articular cartilage repair

Articular cartilage lacks natural healing abilities and necessitates surgical treatments for injuries. While microfracture (MF) is a primary surgical approach, it often results in the formation of unstable fibrocartilage. Delivering hyaline cartilage directly to defects poses challenges due to the limited availability of autologous cartilage and difficulties associated with allogeneic cartilage delivery. We developed a decellularized allogeneic cartilage paste (DACP) using human costal cartilage mixed with a crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC) carrier. The decellularized allogeneic cartilage preserved the extracellular matrix and the nanostructure of native hyaline cartilage. The crosslinked HA-CMC carrier provided shape retention and moldability. In vitro studies confirmed that DACP did not cause cytotoxicity and promoted migration, proliferation, and chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. After 6 months of implantation in rabbit knee osteochondral defects, DACP combined with MF outperformed MF alone, demonstrating improved gait performance, defect filling, morphology, extracellular matrix deposition, and biomechanical properties similar to native cartilage. Thus, DACP offers a safe and effective method for articular cartilage repair, representing a promising augmentation to MF. Statement of significanceDirectly delivering hyaline cartilage to repair articular cartilage defects is an ideal treatment. However, current allogeneic cartilage products face delivery challenges. In this study, we developed a decellularized allogeneic cartilage paste (DACP) by mixing human costal cartilage with crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC). DACP preserves extracellular matrix components and nanostructures similar to native cartilage, with HA-CMC ensuring shape retention and moldability. Our study demonstrates improved cartilage repair by combining DACP with microfracture, compared to microfracture alone, in rabbit knee defects over 6 months. This is the first report showing better articular cartilage repair using decellularized allogeneic cartilage with microfracture, without the need for exogenous cells or bioactive substances.

Chemical Hypoxic Preconditioning Improves Survival and Proliferation of Mesenchymal Stem Cells.

Increasing evidence has demonstrated that mesenchymal stem cells (MSCs) have been linked to tissue regeneration both in vitro and in vivo. However, poor engraftment and low survival rate of transplanted MSCs are still a major concern. It has been found that the proliferation, survival, and migration of MSCs are all increased by hypoxic preconditioning. However, the molecular mechanism through which hypoxic preconditioning enhances these beneficial properties of MSCs remains to be fully investigated. Therefore, the present study is aimed to investigate the mechanism by which hypoxic preconditioning enhances the survival of MSCs. We used proteomic analysis to explore the molecules that may contribute to the survival and proliferation of hypoxic preconditioned (HP) MSCs. The analysis revealed a higher expression of prelamin A/C (Lmna), glutamate dehydrogenase 1(Glud1), Actin, cytoplasmic 1(Actb), Alpha-enolase (Eno1), Glucose-6-phosphate 1-dehydrogenase (G6pd), Protein disulfide-isomerase A3 (Pdia3), Malate dehydrogenase (Mdh1), Peroxiredoxin-6 (Prdx6), Superoxide dismutase (Sod1), and Annexin A2 (Anxa2) in HP-MSCs. These proteins are possibly involved in cellular survival and proliferation through various cellular pathways. This research could aid in understanding the processes involved in hypoxic preconditioning of MSCs and designing of cell-based therapeutic strategies for tissue regeneration.

Plasmonic microcarriers for sensing and cell expansion

Microcarriers (MCs, typically 50–200 µm) are promising growth supports for high-throughput cell expansion, with capability to overcome the limitations of surface area availability and nutrient access encountered by cell culture in 2D well plate configurations. Equipping MCs with in-built capability to sense molecular biomarkers is a key step forward to meet the emerging demands of personalized cell-based therapies. However, integrating sensing functionality into MCs is non-trivial due to fabrication limitations imposed by their large size, curved surfaces, and their suspension in fluid. If achieved, the sensor-integrated MCs should face further concerns of reduced stability and cytocompatibility during cell-culture. Here we demonstrate plasmonic microcarriers (PMCs) that integrate spectroscopic sensing and cell expansion functions through the deposition of gold nanoparticle (AuNP) assemblies on dextran-based MCs. Hydrogel characteristics of the dextran microcarriers was found to profoundly enhance the binding density and kinetics of AuNPs, as seen by attainment of saturated densities in few seconds, and at nanoparticle concentrations only twice that of the surface sites. The approaches to prepare PMCs are distinguished by simple, scalable routes, without need for sophisticated lab infrastructure. The capability of PMCs to act as spectroscopic transducers was demonstrated by surface-enhanced spectroscopic (SERS) detection of a model molecular probe. The growth, proliferation and migration of human mesenchymal stem cells on the PMCs was found to be comparable to that of the uncoated MCs. The results pave the way to smart, multifunctional cell growth supports to interrogate, control and report cell behavior during culture.

Enhanced Cartilage and Subchondral Bone Repair Using Carbon Nanotube-Doped Peptide Hydrogel-Polycaprolactone Composite Scaffolds.

A carbon nanotube-doped octapeptide self-assembled hydrogel (FEK/C) and a hydrogel-based polycaprolactone PCL composite scaffold (FEK/C3-S) were developed for cartilage and subchondral bone repair. The composite scaffold demonstrated modulated microstructure, mechanical properties, and conductivity by adjusting CNT concentration. In vitro evaluations showed enhanced cell proliferation, adhesion, and migration of articular cartilage cells, osteoblasts, and bone marrow mesenchymal stem cells. The composite scaffold exhibited good biocompatibility, low haemolysis rate, and high protein absorption capacity. It also promoted osteogenesis and chondrogenesis, with increased mineralization, alkaline phosphatase (ALP) activity, and glycosaminoglycan (GAG) secretion. The composite scaffold facilitated accelerated cartilage and subchondral bone regeneration in a rabbit knee joint defect model. Histological analysis revealed improved cartilage tissue formation and increased subchondral bone density. Notably, the FEK/C3-S composite scaffold exhibited the most significant cartilage and subchondral bone formation. The FEK/C3-S composite scaffold holds great promise for cartilage and subchondral bone repair. It offers enhanced mechanical support, conductivity, and bioactivity, leading to improved tissue regeneration. These findings contribute to the advancement of regenerative strategies for challenging musculoskeletal tissue defects.

Engineered Extracellular Vesicles for Delivery of an IL-1 Receptor Antagonist Promote Targeted Repair of Retinal Degeneration.

Retinal degeneration (RD) is an irreversible blinding disease that seriously affects patients' daily activities and mental health. Targeting hyperactivated microglia and regulating polarization are promising strategies for treating the disease. Mesenchymal stem cell (MSC) transplantation is proven to be an effective treatment due to its immunomodulatory and regenerative properties. However, the low efficiency of cell migration and integration of MSCs remains a major obstacle to clinical use. The goal of this study is to develop a nanodelivery system that targets hyperactivated microglia and inhibits their release of proinflammatory factors, to achieve durable neuroprotection. This approach is to engineer extracellular vesicles (EVs) isolated from MSC, modify them with a cyclic RGD (cRGD) peptide on their surface, and load them with an antagonist of the IL-1 receptor, anakinra. Comparing with non-engineered EVs, it is observed that engineered cRGD-EVs exhibit an increased targeting efficiency against hyperactivated microglia and strongly protected photoreceptors in experimental RD cells and animal models. This study provides a strategy to improve drug delivery to degenerated retinas and offers a promising approach to improve the treatment of RD through targeted modulation of the immune microenvironment via engineered cRGD-EVs.

IRE1a-Induced FilaminA Phosphorylation Enhances Migration of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients.

Multiple myeloma (MM) is an aggressive malignancy that shapes, during its progression, a pro-tumor microenvironment characterized by altered protein secretion and the gene expression of mesenchymal stem cells (MSCs). In turn, MSCs from MM patients can exert an high pro-tumor activity and play a strong immunosuppressive role. Here, we show, for the first time, greater cell mobility paralleled by the activation of FilaminA (FLNA) in MM-derived MSCs, when compared to healthy donor (HD)-derived MSCs. Moreover, we suggest the possible involvement of the IRE1a-FLNA axis in the control of the MSC migration process. In this way, IRE1a can be considered as a good target candidate for MM therapy, considering its pro-survival, pro-osteoclast and chemoresistance role in the MM microenvironment. Our results suggest that IRE1a downregulation could also interfere with the response of MSCs to MM stimuli, possibly preventing cell-cell adhesion-mediated drug resistance. In addition, further investigations harnessing IRE1a-FLNA interaction could improve the homing efficiency of MSC as cell product for advanced therapy applications.

An engineered biomaterial to harness the differentiation potential of endogenous human gingival mesenchymal stem cells (hGMSCs)

Here, we developed a stromal cell-derived factor-1a (SDF-1α) delivery biomaterial as an artificial polymeric-based niche with the ability to recruit local endogenous human gingival mesenchymal stem cells (hGMSCs) for craniofacial bone regeneration applications. Polydopamine-coated poly(ε-caprolactone) (PCL)-Gelatin electrospun membranes were loaded with stromal cell-derived factor-1α (SDF-1α) via physical adsorption. Subsequently, the release profile of the SDF-1α and chemotactic capacity on human bone marrow mesenchymal stem cells (hBMMSCs) and hGMSCs were evaluated. The osteogenic differentiation capacity of the recruited MSCs was also assessed in vitro. Our results confirmed the sustainable release of SDF-1α from the developed biomaterial promoting the migration and homing of human bone marrow mesenchymal stem cells (hBMMSCs) and hGMSCs. Moreover, the results of the osteogenic differentiation assay showed that SDF-1α delivery significantly enhanced osteogenic differentiation of hBMMSCs and hGMSCs and up-regulated the gene expression of osteogenic markers compared to the control group. In conclusion, the current study successfully developed a novel and effective treatment modality for craniofacial bone regeneration by recruiting the autogenous progenitor cells including hGMSCs. The developed niches can potentially lead to the development of a novel platform for targeted manipulation of in vivo microenvironment to achieve efficient and safe craniofacial cell reprogramming, which also will pave the road to determine the capacity of local hGMSCs' contribution to in situ bone regeneration.

HGF/c-Met signaling promotes the migration and proliferation of deer antler MSCs

The complete regeneration of deer antlers is based on the proliferation and differentiation of stem cells. Mesenchymal stem cells (MSCs) of antlers have an important role in antler regeneration and rapid growth and development. HGF is mainly synthesized and secreted by mesenchymal cells. After binding to its receptor c-Met, which transduces signals into cells to stimulate cell proliferation and migration in various organs to promote tissue morphogenesis and angiogenesis. However, the role and mechanism of the HGF/c-Met signaling pathway on antler MSCs are still unclear. In this study, we established antler MSCs with overexpression and interference of HGF gene by lentivirus and small interference RNA, observed the effect of HGF/c-Met signal pathway on the proliferation and migration of antler MSCs, and detected the expression of downstream related signal pathway genes, to explore the mechanism of HGF/c-MET signal pathway on the proliferation and migration of antler MSCs. The results showed that the HGF/c-Met signal affects the expression of RAS, ERK and MEK genes, regulates the proliferation of pilose antler MSCs through Ras/Raf, MEK/ERK pathway, affects the expression of Gab1, Grb2, AKT and PI3K genes, and regulates the migration of MSCs of pilose antler through Gab1/Grb2 and PI3K/AKT pathway.

3D Printing of Microenvironment-Specific Bioinspired and Exosome-Reinforced Hydrogel Scaffolds for Efficient Cartilage and Subchondral Bone Regeneration.

In clinical practice, repairing osteochondral defects presents a challenge due to the varying biological properties of articular cartilages and subchondral bones. Thus, elucidating how spatial microenvironment-specific biomimetic scaffolds can be used to simultaneously regenerate osteochondral tissue is an important research topic. Herein, a novel bioinspired double-network hydrogel scaffold produced via 3D printing with tissue-specific decellularized extracellular matrix (dECM) and human adipose mesenchymal stem cell (MSC)-derived exosomes is described. The bionic hydrogel scaffolds promote rat bone marrow MSC attachment, spread, migration, proliferation, and chondrogenic and osteogenic differentiation in vitro, as determined based on the sustained release of bioactive exosomes. Furthermore, the 3D-printed microenvironment-specific heterogeneous bilayer scaffolds efficiently accelerate the simultaneous regeneration of cartilage and subchondral bone tissues in a rat preclinical model. In conclusion, 3D dECM-based microenvironment-specific biomimetics encapsulated with bioactive exosomes can serve as a novel cell-free recipe for stem cell therapy when treating injured or degenerative joints. This strategy provides a promising platform for complex zonal tissue regeneration whilst holding attractive clinical translation potential.

Backscatter from therapeutic doses of ionizing irradiation does not impair cell migration on titanium implants in vitro

ObjectiveThe influence of radiation backscatter from titanium on DNA damage and migration capacity of human osteoblasts (OBs) and mesenchymal stem cells (MSCs) may be critical for the osseointegration of dental implants placed prior to radiotherapy. In order to evaluate effects of radiation backscatter, the immediate DNA damage and migration capacity of OBs and MSCs cultured on titanium or plastic were compared after exposure to ionizing irradiation. Materials and methodsHuman OBs and MSCs were seeded on machined titanium, moderately rough fluoride-modified titanium, or tissue culture polystyrene, and irradiated with nominal doses of 2, 6, 10, or 14 Gy. Comet assay was performed immediately after irradiation, while a scratch wound healing assay was initiated 24 h post-irradiation. Fluorescent live cell imaging documented the migration.ResultsDNA damage increased with higher dose and with backscatter from titanium, and MSCs were significantly more affected than OBs. All doses of radiation accelerated the cell migration on plastic, while only the highest dose of 10 Gy inhibited the migration of both cell types on titanium.ConclusionsHigh doses (10 Gy) of radiation inhibited the migration capacity of both cell types on titanium, whereas lower doses (2 and 6 Gy) did not affect the migration of either OBs or MSCs.Clinical relevanceFractionated doses of 2 Gy/day, as distributed in conventional radiotherapy, appear not to cause severe DNA damage or disturb the migration of OBs or MSCs during osseointegration of dental implants.

Multifunctional hydrogel enhances bone regeneration through sustained release of Stromal Cell-Derived Factor-1α and exosomes.

Fracture nonunion remains a great challenge for orthopedic surgeons. Fracture repair comprises of three phases, the inflammatory, repair and remodeling stage. Extensive advancements have been made in the field of bone repair, including development of strategies to balance the M1/M2 macrophage populations, and to improve osteogenesis and angiogenesis. However, such developments focused on only one or the latter two phases, while ignoring the inflammatory phase during which cell recruitment occurs. In this study, we combined Stromal Cell-Derived Factor-1α (SDF-1α) and M2 macrophage derived exosomes (M2D-Exos) with a hyaluronic acid (HA)-based hydrogel precursor solution to synthesize an injectable, self-healing, adhesive HA@SDF-1α/M2D-Exos hydrogel. The HA hydrogel demonstrated good biocompatibility and hemostatic ability, with the 4% HA hydrogels displaying great antibacterial activity against gram-negative E. coli and gram-positive S. aureus and Methicillin-resistant Staphylococcus aureus (MRSA). Synchronously and sustainably released SDF-1α and M2D-Exos from the HA@SDF-1α/M2D-Exos hydrogel enhanced proliferation and migration of human bone marrow mesenchymal stem cell (HMSCs) and Human Umbilical Vein Endothelial Cells (HUVECs), promoting osteogenesis and angiogenesis both in vivo and in vitro. Overall, the developed HA@ SDF-1α/M2D-Exos hydrogel was compatible with the natural healing process of fractures and provides a new modality for accelerating bone repair by coupling osteogenesis, angiogenesis, and resisting infection at all stages.

Decellularized periosteum promotes guided bone regeneration via manipulation of macrophage polarization.

Periosteum has shown potential as an effective barrier membrane for guided bone regeneration (GBR). However, if recognized as a "foreign body," insertion of a barrier membrane in GBR treatment will inevitably alter the local immune microenvironment and subsequently influence bone regeneration. The aim of this investigation was to fabricate decellularized periosteum (DP) and investigate its immunomodulatory properties in GBR. DP was successfully fabricated from periosteum from the mini-pig cranium. In vitro experiments indicated that the DP scaffold modulated macrophage polarization toward a pro-regenerative M2 phenotype, which in turn facilitated migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. A rat GBR model with a cranial critical-size defect was established, and our in vivo experiment confirmed the beneficial effects of DP on the local immune microenvironment and bone regeneration. Collectively, the findings of this study indicate that the prepared DP possesses immunomodulatory properties and represents a promising barrier membrane for GBR procedures.

In Situ Enzymatic Reaction Generates Magnesium-Based Mineralized Microspheres with Superior Bioactivity for Enhanced Bone Regeneration.

Bone is a naturally mineralized tissue with a remarkable hierarchical structure, and the treatment of bone defects remains challenging. Microspheres with facile features of controllable size, diverse morphologies, and specific functions display amazing potentials for bone regeneration. Herein, inspired by natural biomineralization, a novel enzyme-catalyzed reaction is reported to prepare magnesium-based mineralized microspheres. First, silk fibroin methacryloyl (SilMA) microspheres are prepared using a combination of microfluidics and photo-crosslinking. Then, the alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) is successfully used to induce the formation of spherical magnesium phosphate (MgP) in the SilMA microspheres. These SilMA@MgP microspheres display uniform size, rough surface structure, good degradability, and sustained Mg2+ release properties. Moreover, the in vitro studies demonstrate the high bioactivities of SilMA@MgP microspehres in promoting the proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis shows that the osteoinductivity of SilMA@MgP microspheres may be related to the activation of the PI3K/Akt signaling pathway. Finally, the bone regeneration enhancement units (BREUs) are designed and constructed by inoculating BMSCs onto SilMA@MgP microspheres. In summary, this study demonstrates a new biomineralization strategy for designing biomimetic bone repair materials with defined structures and combination functions.

Lyophilized Platelet-Rich Fibrin Exudate-Loaded Carboxymethyl Chitosan/GelMA Hydrogel for Efficient Bone Defect Repair.

Platelet-rich fibrin (PRF) is an autologous growth factor carrier that promotes bone tissue regeneration, but its effectiveness is restrained by poor storage capabilities, uncontrollable concentration of growth factors, unstable shape, etc. Herein, we developed a photocrosslinkable composite hydrogel by incorporating lyophilized PRF exudate (LPRFe) into the carboxymethyl chitosan methacryloyl (CMCSMA)/gelatin methacryloyl (GelMA) hydrogel to effectively solve the dilemma of PRF. The hydrogel possessed suitable physical properties and sustainable release ability of growth factors in LPRFe. The LPRFe-loaded hydrogel could improve the adhesion, proliferation, migration, and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs). Furthermore, the animal experiments demonstrated that the hydrogel possessed excellent biocompatibility and biodegradability, and the introduction of LPRFe in the hydrogel can effectively accelerate the bone healing process. Conclusively, the combination of LPRFe with CMCSMA/GelMA hydrogel may be a promising therapeutic approach for bone defects.

Scalable and Uniform Fabrication of Dexamethasone-Eluting Depot-Engineered Stem Cell Spheroids as a Microtissue Construct to Target Bone Regeneration.

Potentiation of stem cell potency is critical for successful tissue engineering, especially for bone regeneration. Three-dimensional cell culture and bioactive molecule co-delivery with cells have been proposed to achieve this effect. Here, we provide a uniform and scalable fabrication of osteogenic microtissue constructs of mesenchymal stem cell (MSC) spheroids surface-engineered with dexamethasone-releasing polydopamine-coated microparticles (PD-DEXA/MPs) to target bone regeneration. The microparticle conjugation process was rapid and cell-friendly and did not affect the cell viability or key functionalities. The incorporation of DEXA in the conjugated system significantly enhanced the osteogenic differentiation of MSC spheroids, as evidenced by upregulating osteogenic gene expression and intense alkaline phosphatase and alizarin red S staining. In addition, the migration of MSCs from spheroids was tested on a biocompatible macroporous fibrin scaffold (MFS). The result showed that PD-DEXA/MPs were stably anchored on MSCs during cell migration over time. Finally, the implantation of PD-DEXA/MP-conjugated spheroid-loaded MFS into a calvarial defect in a mouse model showed substantial bone regeneration. In conclusion, the uniform fabrication of microtissue constructs containing MSC spheroids with drug depots shows a potential to improve the performance of MSCs in tissue engineering.

The Migration and the Fate of Dental Pulp Stem Cells.

Human dental pulp stem cells (hDPSCs) are adult mesenchymal stem cells (MSCs) obtained from dental pulp and derived from the neural crest. They can differentiate into odontoblasts, osteoblasts, chondrocytes, adipocytes and nerve cells, and they play a role in tissue repair and regeneration. In fact, DPSCs, depending on the microenvironmental signals, can differentiate into odontoblasts and regenerate dentin or, when transplanted, replace/repair damaged neurons. Cell homing depends on recruitment and migration, and it is more effective and safer than cell transplantation. However, the main limitations of cell homing are the poor cell migration of MSCs and the limited information we have on the regulatory mechanism of the direct differentiation of MSCs. Different isolation methods used to recover DPSCs can yield different cell types. To date, most studies on DPSCs use the enzymatic isolation method, which prevents direct observation of cell migration. Instead, the explant method allows for the observation of single cells that can migrate at two different times and, therefore, could have different fates, for example, differentiation and self-renewal. DPSCs use mesenchymal and amoeboid migration modes with the formation of lamellipodia, filopodia and blebs, depending on the biochemical and biophysical signals of the microenvironment. Here, we present current knowledge on the possible intriguing role of cell migration, with particular attention to microenvironmental cues and mechanosensing properties, in the fate of DPSCs.

Titanium surface interacting with blood clot enhanced migration and osteogenic differentiation of bone marrow mesenchymal stem cells.

Introduction: Blood clot formation is the initial phase upon implantation, and the feature of blood clot orchestrates the following complement system activation, coagulation cascade, and bone marrow mesenchymal stromal cells (BMSCs) recruitment. This study aimed to investigate the effect of implant surface on blood-material interactions and subsequent BMSC cellular behaviors. Methods: This study was established to imitate the physiological process of implantation in vivo and in vitro. Whole blood was incubated with polished titanium (PT) surfaces and sandblasted and double acid-etching (SLA) surfaces for 10min or 2h, then seeded with BMSCs. The adhesion, proliferation, migration, and differentiation of cells were studied at specific time points. Titanium implants were implanted into the tibia in vivo and were screwed out after implantation. The activation of the coagulation cascade, platelets, complement system, and clot networks were assessed and further quantitatively analyzed. Results: Compared with the PT surface, the SLA surface induced the earlier and stronger blood coagulation cascade and formed a more stratified clots network with fibrinogen, platelets, and CD14 positive cell. The adhesion, proliferation, and migration of BMSCs were enhanced by pre-incubated surfaces. The higher levels of the osteogenic-related genes, ALP activity, and calcium nodule formation were showed on SLA surfaces with blood incubation. Conclusion: SLA titanium surfaces play a role in influencing the formation of blood clots and coordinating surface-blood interactions and cell biological processes. These findings provide the idea of modifying the blood clots formed on the implant surface by biomaterials modification and thus has implications for the development of better osteogenic biomaterials.

Hypoxia regulates adipose mesenchymal stem cells proliferation, migration, and nucleus pulposus-like differentiation by regulating endoplasmic reticulum stress via the HIF-1α pathway

ObjectiveHypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation.MethodADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions.ResultThe cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed.ConclusionHypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration.

Therapeutic Efficacy and Migration of Mesenchymal Stem Cells after Intracerebral Transplantation in Rats with Experimental Ischemic Stroke.

We studied therapeutic efficacy and migration characteristics of mesenchymal stem cells isolated from the human placenta after their intracerebral (stereotactic) administration to rats with the experimental ischemic stroke. It was shown that cell therapy significantly improved animal survival rate and reduced the severity of neurological deficit. New data on the migration pathways of transplanted cells in the brain were obtained.