Regenerative Medicine Strategies Research Articles

Loss of regulation of protein synthesis and turnover underpins an attenuated stress response in senescent human mesenchymal stem cells

Cells respond to stress by synthesizing chaperone proteins that seek to correct protein misfolding and maintain function. However, abrogation of protein homeostasis is a hallmark of aging, leading to loss of function and the formation of proteotoxic aggregates characteristic of pathology. Consequently, discovering the underlying molecular causes of this deterioration in proteostasis is key to designing effective interventions to disease or to maintaining cell health in regenerative medicine strategies. Here, we examined primary human mesenchymal stem cells, cultured to a point of replicative senescence and subjected to heat shock, as an invitro model of the aging stress response. Multi -omics analysis showed how homeostasis components were reduced in senescent cells, caused by dysregulation of a functional network of chaperones, thereby limiting proteostatic competence. Time-resolved analysis of the primary response factors, including those regulating heat shock protein 70 kDa (HSPA1A), revealed that regulatory control is essentially translational. Senescent cells have a reduced capacity for chaperone protein translation and misfolded protein (MFP) turnover, driven by downregulation of ribosomal proteins and loss of the E3 ubiquitin ligase CHIP (C-terminus of HSP70 interacting protein) which marks MFPs for degradation. This limits the cell's stress response and subsequent recovery. A kinetic model recapitulated these reduced capacities and predicted an accumulation of MFP, a hypothesis supported by evidence of systematic changes to the proteomic fold state. These results thus establish a specific loss of regulatory capacity at the protein, rather than transcript, level and uncover underlying systematic links between aging and loss of protein homeostasis.

Construction, Characterization, and Regenerative Application of Self-Assembled Human Mesenchymal Stem Cell Aggregates.

Mesenchymal stem cells (MSCs), characterized by their self-renewal ability and multilineage differentiation potential, can be derived from various sources and are emerging as promising candidates for regenerative medicine, especially for regeneration of the tooth, bone, cartilage, and skin. The self-assembled approach of MSC aggregation, which notably constructs cell clusters mimicking the developing mesenchymal condensation, allows high-density stem cell delivery along with preserved cell-cell interactions and extracellular matrix (ECM) as the microenvironment niche. This method has been shown to enable efficient cell engraftment and survival, thus promoting the optimized application of exogenous MSCs in tissue engineering and safeguarding clinical organ regeneration. This paper provides a detailed protocol for the construction and characterization of self-assembled aggregates based on umbilical cord mesenchymal stem cells (UCMSCs), as well as an example of the cranial bone regenerative application. The implementation of this procedure will help guide the establishment of an efficient MSC transplantation strategy for tissue engineering and regenerative medicine.

Decellularized Tissue-Induced Cellular Recruitment for Tissue Engineering and Regenerative Medicine.

Biomaterials that recapitulate the native in vivo microenvironment are promising to facilitate tissue repair and regeneration when used in combination with relevant growth factors (GFs), chemokines, cytokines, and other small molecules and cell sources. However, limitations with the use of exogenous factors and ex vivo cell expansion has prompted cell-/GF-free tissue engineering strategies. Additionally, conventional chemotaxis assays for studying cell migration behavior provide limited information, lack long-term stability, and fail to recapitulate physiologically relevant conditions. In this study, articular cartilage tissue-based biomaterials were developed via a rapid tissue decellularization protocol. The decellularized tissue was further processed into a hydrogel through solubilization and self-assembly. Chemotactic activity of the tissue-derived gel was investigated using sophisticated cellular migration assays. These tissue-derived extracellular matrix (ECM) biomaterials retain biochemical cues of native tissue and stimulate the chemotactic migration of hBMSCs in 2D and 3D cell migration models using a real-time chemotaxis assay. This strategy, in a way, developed a new paradigm in tissue engineering where cartilage tissue repair and regeneration can be approached with decellularized cartilage tissue in the place of an engineered matrix. This strategy can be further expanded for other tissue-based ECMs to develop cell-/GF-free tissue engineering and regenerative medicine strategies for recruiting endogenous cell populations to facilitate tissue repair and regeneration.

Role of secretomes in cell-free therapeutic strategies in regenerative medicine.

After an injury, peripheral nervous system neurons have the potential to rebuild their axons by generating a complicated activation response. Signals from the damaged axon are required for this genetic transition to occur. Schwann cells (SCs) near a damaged nerve's distal stump also play a role in the local modulation of axonal programs, not only via cell-to-cell contacts but also through secreted signals (the secretome). The secretome is made up of all the proteins that the cell produces, such as cytokines, growth factors, and extracellular vesicles. The released vesicles may carry signaling proteins as well as coding and regulatory RNAs, allowing for multilayer communication. The secretome of SCs is now well understood as being critical for both orchestrating Wallerian degeneration and maintaining axonal regeneration. As a consequence, secretome has emerged as a feasible tissue regeneration alternative to cell therapy. Separate SC secretome components have been used extensively in the lab to promote peripheral nerve regeneration after injury. However, in neurological therapies, the secretome generated by mesenchymal (MSC) or other derived stem cells has been the most often used. In fact, the advantages of cell treatment have been connected to the release of bioactive chemicals and extracellular vesicles, which make up MSCs' secretome.

Unveiling the Assembly of Neutral Marine Polysaccharides into Electrostatic-Driven Layer-by-Layer Bioassemblies by Chemical Functionalization

Marine-origin polysaccharides, in particular cationic and anionic ones, have been widely explored as building blocks in fully natural or hybrid electrostatic-driven Layer-by-Layer (LbL) assemblies for bioapplications. However, the low chemical versatility imparted by neutral polysaccharides has been limiting their assembly into LbL biodevices, despite their wide availability in sources such as the marine environment, easy functionality, and very appealing features for addressing multiple biomedical and biotechnological applications. In this work, we report the chemical functionalization of laminarin (LAM) and pullulan (PUL) marine polysaccharides with peptides bearing either six lysine (K6) or aspartic acid (D6) amino acids via Cu(I)-catalyzed azide-alkyne cycloaddition to synthesize positively and negatively charged polysaccharide-peptide conjugates. The successful conjugation of the peptides into the polysaccharide's backbone was confirmed by proton nuclear magnetic resonance and attenuated total reflectance Fourier-transform infrared spectroscopy, and the positive and negative charges of the LAM-K6/PUL-K6 and LAM-D6/PUL-D6 conjugates, respectively, were assessed by zeta-potential measurements. The electrostatic-driven LbL build-up of either the LAM-D6/LAM-K6 or PUL-D6/PUL-K6 multilayered thin film was monitored in situ by quartz crystal microbalance with dissipation monitoring, revealing the successful multilayered film growth and the enhanced stability of the PUL-based film. The construction of the PUL-peptide multilayered thin film was also assessed by scanning electron microscopy and its biocompatibility was demonstrated in vitro towards L929 mouse fibroblasts. The herein proposed approach could enable the inclusion of virtually any kind of small molecules in the multilayered assemblies, including bioactive moieties, and be translated into more convoluted structures of any size and geometry, thus extending the usefulness of neutral polysaccharides and opening new avenues in the biomedical field, including in controlled drug/therapeutics delivery, tissue engineering, and regenerative medicine strategies.

Microenvironmental modulation in tandem with human stem cell transplantation enhances functional recovery after chronic complete spinal cord injury

While rapid advancements in regenerative medicine strategies for spinal cord injury (SCI) have been made, most research in this field has focused on the early stages of incomplete injury. However, the majority of patients experience chronic severe injury; therefore, treatments for these situations are fundamentally important. Here, we hypothesized that environmental modulation via a clinically relevant hepatocyte growth factor (HGF)-releasing scaffold and human iPS cell-derived neural stem/progenitor cells (hNS/PCs) transplantation contributes to functional recovery after chronic complete transection SCI. Effective release of HGF from a collagen scaffold induced progressive axonal elongation and increased grafted cell viability by activating microglia/macrophages and meningeal cells, inhibiting inflammation, reducing scar formation, and enhancing vascularization. Furthermore, hNS/PCs transplantation enhanced endogenous neuronal regrowth, the extension of graft axons, and the formation of circuits around the lesion and lumbar enlargement between host and graft neurons, resulting in the restoration of locomotor and urinary function. This study presents an effective therapeutic strategy for severe chronic SCI and provides evidence for the feasibility of regenerative medicine strategies using clinically relevant materials.

Mesenchymal stem cells express epidermal markers in an in vitro reconstructed human skin model.

Introduction: In skin traumas, such as burns, epidermal homeostasis is affected, often requiring clinical approaches. Different therapeutic strategies can be used including transplantation, besides the use of synthetic or natural materials with allogeneic cells. In this context, tissue engineering is an essential tool for skin regeneration, and using mesenchymal stem cells (MSC) from the umbilical cord appears to be a promising strategy in regenerative medicine due to its renewal and differentiation potential and hypo immunogenicity. We evaluated the transdifferentiation of MSC from umbilical cord into keratinocytes in three-dimensional (3D) in vitro skin models, using dermal equivalents composed by type I collagen with dermal fibroblasts and a commercial porcine skin decellularized matrix, both cultured at air-liquid interface (ALI). Methods: The expression of epidermal proteins cytokeratins (CK) 5, 14 and 10, involucrin and filaggrin was investigated by real-time PCR and immunofluorescence, in addition to the activity of epidermal kallikreins (KLK) on the hydrolysis of fluorogenic substrates. Results and discussion: The cultivation of MSCs with differentiation medium on these dermal supports resulted in organotypic cultures characterized by the expression of the epidermal markers CK5, CK14, CK10 and involucrin, mainly on the 7th day of culture, and filaggrin at 10th day in ALI. Also, there was a 3-fold increase in the KLK activity in the epidermal equivalents composed by MSC induced to differentiate into keratinocytes compared to the control (MSC cultivated in the proliferation medium). Specifically, the use of collagen and fibroblasts resulted in a more organized MSC-based organotypic culture in comparison to the decellularized matrix. Despite the non-typical epithelium structure formed by MSC onto dermal equivalents, the expression of important epidermal markers in addition to the paracrine effects of these cells in skin may indicate its potential use to produce skin-based substitutes.

Platelet-rich Fibrin versus Platelet-rich Plasma: A Study to Assess Efficacy as a Regenerative Medicine Strategy for Chronic Cutaneous Ulcers.

The management of nonhealing ulcers has been a major challenge clinically. Current therapies include debridement, offloading, etc., which show a poor response. Newer modalities include stem cells, platelet-derived growth factors, and fibrin glues, which reduce healing time. Platelets play a major role in wound healing through the secretion of growth factors, chemokines, etc. and have been an area of interest as a modality in regenerative medicine. The aim was to study the comparative efficacy of autologous platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) as a regenerative medicine strategy for chronic cutaneous ulcers. Forty-four ulcers of duration greater than six weeks were enrolled for a comparative study comprising two groups, each divided either into group A receiving PRF dressings or group B receiving PRP dressing for six weeks. The ulcer evaluation was performed at baseline, each weekly dressing, and a two-week follow-up. Primary efficacy was assessed by the percentage reduction in the volume of ulcers and re-epithelization at eight weeks. In total, 95.2% of ulcers in group A and 90.4% of ulcers in group B showed complete re-epithelization. One ulcer in group A and two ulcers in group B developed an infection. The recurrence of the ulcer was seen in four ulcers in the PRF group and three ulcers in the PRP group. Dressings done with PRF and PRP showed similar efficacy in the percentage reduction in the volume and re-epithelization of chronic cutaneous ulcers. Both dressings were associated with similar complications. PRF and PRP dressings provide a safe, efficacious, and inexpensive regenerative medicine strategy in the healing of chronic cutaneous ulcers.

Clinical usage of dental stem cells and their derived extracellular vesicles.

Stem cell-based therapies remain at the forefront of tissue engineering and regenerative medicine because stem cells are a unique cell source with enormous potential to treat incurable diseases and even extend lifespans. The search for the best stem cell candidates continues to evolve and in recent years, dental stem cells have received significant attention due to their easy accessibility, high plasticity, and multipotential properties. Dental stem cells have been the subject of extensive research in both animal models and human clinical trials over the past two decades, and have demonstrated significant potential in ocular therapy, bone tissue engineering, and, of course, therapeutic applications in dentistry such as regenerative endodontics and periodontal tissue regeneration. These new sources of cells may be advantageous for cellular therapy and the advancement of regenerative medicine strategies, such as allogeneic transplantation or therapy with extracellular vesicles (EVs), which are functional nanoscale membrane vesicles produced by cells. This chapter discusses the accumulating research findings on cell-based regenerative therapy utilizing dental stem cells and their derived EVs, which could be a viable tool for the treatment of a variety of diseases and hence extremely valuable to mankind in the long run.

Regenerative medicine: going beyond transplantology

Since the possibilities of transplantology are limited, there is a need for tissue engineering and regenerative medicine (RM). Several high-tech approaches are used in RM: the use of soluble molecules, gene therapy, stem cell transplantation, tissue engineering, reprogramming of cells and tissues, etc. As an important component, RM strategies include innovative materials that can imitate the extracellular matrix of tissues, influencing the behavior of cells and regulating the structure and function of the formed tissue, for example, 3D polymer scaffolds, bioglass grafts, and nanofiber meshes. There is also no-scaffold tissue engineering, for example, the formation of cell sheets and the cultivation of cells capable of self-organization into appropriate sub-organ structures (intestinal crypts, kidney nephrons, and lung alveoli). In the direction of cell-free RM, the attention of scientists is attracted by exosomes – microvesicles of cellular origin sized 40-100 nm. They can carry a “cargo” of proteins, lipids, RNA, and DNA. Exosomes have the potential for use in the treatment of neurodegenerative, infectious, musculoskeletal, and cardiovascular diseases. Due to their physiological nature, exosomes have very low immunogenicity and the potential to pass through the blood-brain barrier. For the further development of exosomal therapy, it is necessary to improve the methods of their isolation and purification, as well as research on efficiency, safety, pharmacokinetics and pharmacodynamics. An important source of cells for RM is represented by mesenchymal stem cells, which are able to differentiate into almost any cell line and exert anti-inflammatory, immunoregulatory and immunosuppressive effects.

Stem cell-derived exosomes in the treatment of melasma and its percutaneous penetration.

Melasma is a refractory skin disease due to its complex pathogenesis and difficult treatment. Studies have found that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) could serve as a novel cell-free therapeutic strategy in regenerative and esthetic medicine. It could potentially treat melasma, but the skin barrier is a challenge. In this study, we aim to explore the safety and efficacy of hUCMSC-Exos in the treatment of melasma and the means to promote its percutaneous penetration. In the animal study about the effect of penetration, percutaneous penetration of PKH67-labeled hUCMSC-Exos was studied under microneedles, 1565 nm nonablative fractional laser (NAFL), and a plasma named Peninsula Blue Aurora Shumin Master (PBASM) treatments, observed by confocal laser scanning microscopy. In the clinical application study, 60 patients with melasma treated in our department were divided into four groups. NAFL combined with normal saline treatment was used for Group A. Microneedles, NAFL, and PBASM combined with hUCMSC-Exos treatments were used for Groups B, C, and D, respectively. Each patient received four treatments at 1-month intervals. Assessments were done using the degree of pain posttreatment, melasma area and severity score, improvement rate, physician global assessment score, satisfaction, and complications. In the animal study about the effect of penetration, hUCMSC-Exos can penetrate the deep dermis under microneedles, NAFL, and PBASM treatments. In the clinical application study, compared with Group A, Groups B, C, and D showed significantly improved therapeutic effect and patient satisfaction (p < 0.05), and there was no significant difference among Groups B, C, and D.(p > 0.05). Patients in Group B reported higher pain levels than those in the other three groups (p < 0.05); the treatment experience of patients in Group D was better. hUCMSC-Exos can improve the symptoms of melasma safely and effectively. Compared with microneedles, NAFL and PBASM can also achieve a good effect toward promoting penetration. These findings are worthy of exploration and clinical application.

Hydrogel viscoelasticity modulates migration and fusion of mesenchymal stem cell spheroids.

Multicellular spheroids made of stem cells can act as building blocks that fuse to capture complex aspects of native in vivo environments, but the effect of hydrogel viscoelasticity on cell migration from spheroids and their fusion remains largely unknown. Here, we investigated the effect of viscoelasticity on migration and fusion behavior of mesenchymal stem cell (MSC) spheroids using hydrogels with a similar elasticity but different stress relaxation profiles. Fast relaxing (FR) matrices were found to be significantly more permissive to cell migration and consequent fusion of MSC spheroids. Mechanistically, inhibition of ROCK and Rac1 pathways prevented cell migration. Moreover, the combination of biophysical and biochemical cues provided by fast relaxing hydrogels and platelet-derived growth factor (PDGF) supplementation, respectively, resulted in a synergistic enhancement of migration and fusion. Overall, these findings emphasize the important role of matrix viscoelasticity in tissue engineering and regenerative medicine strategies based on spheroids.

Rapid fabrication and screening of tailored functional 3D biomaterials: Validation in bone tissue repair – Part II

Regenerative medicine strategies place increasingly sophisticated demands on 3D biomaterials to promote tissue formation at sites where tissue would otherwise not form. Ideally, the discovery/fabrication of the 3D scaffolds needs to be high-throughput and uniform to ensure quick and in-depth analysis in order to pinpoint appropriate chemical and mechanical properties of a biomaterial. Herein we present a versatile technique to screen new potential biocompatible acrylate-based 3D scaffolds with the ultimate aim of application in tissue repair. As part of this process, we identified an acrylate-based 3D porous scaffold that promoted cell proliferation followed by accelerated tissue formation, pre-requisites for tissue repair. Scaffolds were fabricated by a facile freeze-casting and an in-situ photo-polymerization route, embracing a high-throughput synthesis, screening and characterization protocol. The current studies demonstrate the dependence of cellular growth and vascularization on the porosity and intrinsic chemical nature of the scaffolds, with tuneable 3D scaffolds generated with large, interconnected pores suitable for cellular growth applied to skeletal reparation. Our studies showed increased cell proliferation, collagen and ALP expression, while chorioallantoic membrane assays indicated biocompatibility and demonstrated the angiogenic nature of the scaffolds. VEGRF2 expression in vivo observed throughout the 3D scaffolds in the absence of growth factor supplementation demonstrates a potential for angiogenesis. This novel platform provides an innovative approach to 3D scanning of synthetic biomaterials for tissue regeneration.

A Comprehensive Review of Electrospun Fibers, 3D-Printed Scaffolds, and Hydrogels for Cancer Therapies.

Anticancer therapies and regenerative medicine are being developed to destroy tumor cells, as well as remodel, replace, and support injured organs and tissues. Nowadays, a suitable three-dimensional structure of the scaffold and the type of cells used are crucial for creating bio-inspired organs and tissues. The materials used in medicine are made of non-degradable and degradable biomaterials and can serve as drug carriers. Developing flexible and properly targeted drug carrier systems is crucial for tissue engineering, regenerative medicine, and novel cancer treatment strategies. This review is focused on presenting innovative biomaterials, i.e., electrospun nanofibers, 3D-printed scaffolds, and hydrogels as a novel approach for anticancer treatments which are still under development and awaiting thorough optimization.

Regenerative medicine strategies for hair growth and regeneration: A narrative review of literature.

Hair loss, or alopecia, is associated with several psychosocial and medical comorbidities, and it remains an economic burden to individuals and the society. Alopecia is attributable to varied mechanisms and features a multifactorial predisposition, and the available conventional medical interventions have several limitations. Thus, several therapeutic strategies for alopecia in regenerative medicine are currently being explored, with increasing evidence suggesting that mesenchymal stem cell (MSC) implantation, MSC-derived secretome treatment, and blood-derived platelet-rich plasma therapies are potential treatment options. In this review, we searched the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus using various combinations of terms, such as "stem cell," "alopecia," "hair loss," "Androgenetic alopecia," "male-pattern hair loss," "female-pattern hair loss," "regenerative hair growth," "cell therapy," "mesenchymal stem cells," "MSC-derived extracellular vesicles," "MSC-derived exosomes," and "platelet-rich plasma" and summarized the most promising regenerative treatments for alopecia. Moreover, further opportunities of improving efficacy and innovative strategies for promoting clinical application were discussed.

Single-cell profiling reveals a potent role of quercetin in promoting hair regeneration.

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.

Does Melatonin Associated with Nanostructured Calcium Phosphate Improve Alveolar Bone Repair?

Background and objectives: Calcium phosphates have been widely used as bone substitutes, but their properties are limited to osteoconduction. The association of calcium phosphates with osteoinductive bioactive molecules has been used as a strategy in regenerative medicine. Melatonin has been studied due to its cell protection and antioxidant functions, reducing osteoclastic activity and stimulating newly formed bone. This study aimed to evaluate the effect of topical application of melatonin associated with nanostructured carbonated hydroxyapatite microspheres in the alveolar bone repair of Wistar rats through histological and histomorphometric analysis. Materials and Methods: Thirty female Wistar rats (300 g) were used, divided randomly into three experimental groups (n = 10), G1: nanostructured carbonated hydroxyapatite microspheres associated with melatonin gel (CHA-M); G2: nanostructured carbonated hydroxyapatite (CHA); G3: blood clot (without alveolar filling). The animals were euthanized after 7 and 42 days of the postoperative period and processed for histological and histomorphometric evaluation. Kruskal-Wallis and Dunn's post-test were applied to investigate statistical differences between the groups at the same time point for new bone and connective tissue variables. Mann-Whitney was used to assess statistical differences between different time points and in the biomaterial variable. Results: Results showed a greater volume of residual biomaterial in the CHA-M than the CHA group (p = 0.007), and there were no significant differences in terms of newly formed bone and connective tissue between CHA and CHA-M after 42 days. Conclusions: This study concluded that both biomaterials improved alveolar bone repair from 7 to 42 days after surgery, and the association of CHA with melatonin gel reduced the biomaterial's biodegradation at the implanted site but did not improve the alveolar bone repair.

Future perspective of stem cell-derived exosomes: Cell-free therapeutic strategies for retinal degeneration

With continued expansion of the aged population, the number of patients with retinal degeneration, which is a leading cause of vision loss worldwide, is growing. Stem cell therapies offer hope for regeneration and repair of damaged retinal tissue. Recent reports have highlighted stem cell-derived paracrine mediators, such as exosomes, which appear to exert a therapeutic benefit similar to their cell of origin and do not carry the risk of cell transplantation. One speculated role is that exosomes likely mediate intercellular communication and material exchange. This review depicts the molecular mechanisms underlying exosome-based therapy, especially in retina degeneration diseases. In the future, the use of stem cell-derived exosomes could be considered a novel and cell-free therapeutic strategy in regenerative medicine.

Drug-preloadable methacrylated gelatin microspheres fabricated using an aqueous two-phase system

Gelatin microspheres (GMS) can retain biomolecules and be incorporated into artificial tissues and organs for tissue regeneration. However, the inactivation of biomolecules during the conventional fabrication process of GMS requires postloading of biomolecules to prefabricated GMS. Herein, a novel method for fabricating drug-preloaded GMS using a water-in-water (w/w) emulsification technique, is reported. A highly concentrated gelatin methacrylate (Gm) solution containing fibroblast growth factor 2 (FGF2), a model drug, was emulsified in a highly concentrated polyethylene glycol solution, and the mixture was irradiated with ultraviolet light. The obtained water-in-water gelatin methacrylate microspheres (w/w GmMS) were superior to conventional GMS in terms of stability, FGF2-loading efficiency, and sustained release of FGF2. The FGF2-loaded w/w GmMS efficiently activated the proliferation of adipose tissue-derived mesenchymal stem cells (ASCs). In addition, FGF2-loaded w/w GmMS incorporated into multicellular spheroids of ASCs increased the viability of ASCs in the spheroids. The therapeutic efficacy of ASC spheroids in a wound healing mouse model was significantly improved by the incorporation of FGF2-loaded w/w GmMS. These results indicate that drug-preloadable w/w GmMS can be widely applied in tissue engineering and regenerative medicine strategies.

Meet the First Authors.

HomeCirculation ResearchVol. 131, No. 10Meet the First Authors Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBMeet the First Authors Originally published27 Oct 2022https://doi.org/10.1161/RES.0000000000000580Circulation Research. 2022;131:790–791Sox17 Deficiency Promotes PAH via c-Met Activation (p 792)Download figureDownload PowerPointDr Chan Soon Park is a clinical fellow in the Division of Cardiology at Seoul National University Hospital (SNUH). He earned his BS and MS in Medicine from Seoul National University and his PhD in Medical Science and Engineering from Korea Advanced Institute of Science and Technology (KAIST). During the PhD program in Graduate School of Medical Science and Engineering in KAIST, he was able to learn basic and translational research, the importance of which has been increasingly emphasized in the development of novel and clinically relevant therapeutic strategies in the field of cardiology. Dr Park continues to expand his research in the roles of endothelial cells in various cardiovascular diseases (CVDs) beyond pulmonary arterial hypertension. He also has interests in clinical research, including the association between metabolic profiles and CVDs as well as the role of imaging in CVD risk stratification. Outside of work, he enjoys hiking and spending time with his family.Prohibitin2 Maintains VSMC Contractile Phenotype (p 807)Download figureDownload PowerPointDr Yiting Jia is a postdoctoral fellow at Peking University Health Science Center (PI: Dr Wei Kong and Dr Caihong Yun). He earned his PhD from Peking University. His early experience in research was focused on metabolism reprogramming, lysosome biology and cardiovascular diseases. Now he is gearing up to become an independent research investigator. Outside of work, he enjoys soccer, tennis and listening to music.Download figureDownload PowerPointDr Chenfeng Mao is a research associate at the Beijing Institute of Biotechnology in Beijing, China. He earned a PhD in human physiology from the Department of Physiology and Pathophysiology in Peking University (mentor, Dr Wei Kong). His research focuses on extracellular matrix microenvironment on vascular remodeling during physiological and disease state. Outside of work he enjoys playing badminton.MED1, BMP/TGF-β and Pulmonary Hypertension (p 828)Download figureDownload PowerPointDr Chen Wang earned her PhD from Xi’ an Jiaotong University. During her PhD studies, she was also trained in the laboratory of Dr Ingrid Fleming at the Institute of Vascular Research, Goethe University. Her research focuses on endothelial dysfunction involved in vascular diseases. She was awarded the “Paul Dudley White International Scholar” from ATVB in 2022 and has published several first-author papers including in Circulation and Circulation Research. Her career goal is to become a physician scientist working on cardiovascular diseases and related translational research. Outside of work, she enjoys traveling, music and baking.Download figureDownload PowerPointYuanming Xing is a PhD candidate in internal medicine at Xi’an Jiaotong University. She also studied computational biology at Warshel Institute for Computational Biology at the Chinese University of Hong Kong-Shenzhen. She is interested in endothelial function in cardiovascular diseases and has published several papers in the related fields. Her career plan is to become a physician who is also proficient in computational biology. She enjoys learning new things, especially what she may not be good at. In her spare time, she has a passion for animal rescue, computer programming and painting.Intrapericardial Exosomes Repair Heart via Foxo3 (p e135)Download figureDownload PowerPointDr Dashuai Zhu is a postdoctoral research fellow in the BioTherapeutics Lab, headed by Dr Ke Cheng (UNC Chapel Hill and North Carolina State University). Dashuai earned his PhD from the Nankai University, China, where he started his career on cardiac repair using tissue engineering and biomedical engineering approaches. His research focuses on regenerative medicine approaches for the treatment of heart disease, with a particular interest in cell and cell-free therapies for myocardial infarction and heart failure. He can be found on Twitter @das_zhu.Download figureDownload PowerPointDr Ke Huang is an assistant research professor in the Department of Molecular Biomedical Sciences at North Carolina State University. He earned his MD in 2008 from Shanxi Medical University and PhD from North Carolina State University. His postdoctral training was at Duke University. His research focuses on regenerative medicine strategies with a particular interest in adult stem cells, biomaterials and nanomedicine approaches. He can be found on [email protected] Previous Back to top Next FiguresReferencesRelatedDetails October 28, 2022Vol 131, Issue 10 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000580PMID: 36302055 Originally publishedOctober 27, 2022 PDF download Advertisement SubjectsAgingCardiovascular DiseaseExercise