Regenerative Therapy

Application of mesenchymal stem cells for neurodegenerative diseases therapy discovery
Trinh QD, Mai HN and Pham DT
Neurodegenerative diseases are central or peripheral nervous system disorders associated with progressive brain cell degeneration. Common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis have been widely studied. However, current therapeutics only reduce the symptoms and do not ameliorate the pathogenesis of these diseases. Recent studies suggested the roles of neuroinflammation, apoptosis, and oxidative stress in neurodegenerative diseases. Mesenchymal stem cells (MSCs) exert anti-apoptotic, anti-inflammatory, and antioxidative effects. Therefore, investigating the effects of MSCs and their applications may lead to the discovery of more effective therapies for neurodegenerative diseases. In this study, we review different approaches used to identify therapies for neurodegenerative diseases using MSCs.
In vivo biocompatibility assessment of 3D printed bioresorbable polymers for brain tissue regeneration. A feasibility study
Clauzel J, Colitti N, Combeau M, Labriji W, Robert L, Brilhault A, Cirillo C, Desmoulin F, Raymond-Letron I and Loubinoux I
The limited capacity of brain tissue to regenerate after acute injury, hampered by cell death, edema and inflammation, has led to an interest in promising and innovative approaches such as implantable regenerative scaffolds designed to improve brain plasticity. Leveraging the capabilities of bioprinting, these scaffolds can be tailored to match the intricate architecture of the brain.
Adipogenesis of bioabsorbable implants under irradiation in a rodent model
Lee S, Ogino S, Inoue M, Nakano T, Kato Y, Sakamoto M, Mizowaki T, Yamaoka T and Morimoto N
Breast cancer is the most common cancer among women. Partial mastectomy is an alternative to mastectomy in early-stage breast cancer to restore a poor quality of life (QOL). However, the aesthetic satisfaction with this procedure is inadequate. The standard methods for breast reconstruction have certain limitations. We developed bioabsorbable implants consisting of an outer mesh composed of poly L-lactic acid (PLLA) and an inner component filled with a collagen sponge (CS). These implants were designed to promote and sustain adipogenesis in vivo, without the addition of exogenous cells or growth factors. In this study, we used PLLA mesh implants to investigate the effects of irradiation on fat formation, which is important in partial mastectomy.
Regulatory insights on advanced CAR-T cell products, AAV-based Gene therapies, and medical care/practice in cell and Gene therapies: Report from the 6th Asia partnership conference of regenerative medicine- April 20, 2023
Karasawa H, Mizoguchi H, Choi B, Hsieh CL, Miyano M, Moriya Y, Muthusamy S, Takakura K, Suzuki K, Tsurumaki Y, Watanabe T, Wen K, Yoneda T, Yuan TT and Nomura M
The 6th Asia Partnership Conference of Regenerative Medicine (APACRM) was held in person with online on April 20, 2023, to promote the regulatory harmonization of regenerative medicine products throughout Asia. Recognizing domestic regulatory guidelines within each country and region and the underlying rationales are important initial steps toward harmonizing regulations. The 6th APACRM featured an open dialog regarding non-clinical evaluation for advanced CAR-T products, regulation of clinical trials for AAV-based gene therapies, and cell and gene therapies provided to patients as medical care/medical practices without market authorization through presentations from the industry and panel discussions with regulatory agencies. The latest updates on regenerative medicine in each country and region are introduced. This paper summarizes the proceedings of the 6th APACRM for public dissemination to foster future discussions.
The effects of local delivery of laurus nobilis extract and adipose derived stem cells via electrospun gelatin scaffold on spinal cord injury inflammatoradscy response and its regeneration
Zhang C, Zhang J, Xie D, Guo G and Jalili S
When subjected to injury, the spinal cord's inherent complexity poses significant challenges for effective healing. In this study, gelatin nanofibers loaded with Laurus nobilis extract were developed to serve as a delivery system for adipose-derived stem cells (ADSCs), aiming to explore its potential immunomodulatory effects in a rat model of spinal cord injury. Through a series of in vitro assessments including scanning electron microscopy imaging, cell viability, anti-inflammatory, cell adhesion, biodegradation, and hemocompatibility assays, the characteristics of the delivery system were thoroughly evaluated. The in vitro studies revealed both the biocompatibility of the scaffolds and their notable anti-inflammatory properties, laying the groundwork for further investigation. Subsequent in vivo experiments demonstrated that rats treated with Laurus nobilis extract and ADSCs loaded scaffolds exhibited heightened functional recovery (BBB score of 14.66 ± 1.52 % and hot plate latency time of 8.33 0.26 s) and histological restoration at the 8-week mark post-injury. Notably, ELISA assay results revealed a significant reduction in tissue expression levels of key pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, suggesting a pronounced immunomodulatory effect of the Laurus nobilis extract-loaded scaffolds. The findings underscore the potential of this novel delivery system to improve clinical outcomes in spinal cord injury by enhancing functional recovery and reducing inflammation. This approach could lead to the development of new, natural-based therapeutic strategies for spinal cord injury, with potential extensions to other inflammatory or degenerative conditions. Future research should focus on optimizing this strategy in larger animal models and eventually translating these findings into human clinical trials.
Extracellular vesicles originating from the mechanical microenvironment in the pathogenesis and applications for cardiovascular diseases
Zeng Y, Cui X, Li H, Wang Y, Cheng M and Zhang X
The mechanical microenvironment plays a crucial regulatory role in the growth and development of cells. Mechanical stimuli, including shear, tensile, compression, and extracellular matrix forces, significantly influence cell adhesion, migration, proliferation, differentiation, and various other cellular functions. Extracellular vesicles (EVs) are involved in numerous physiological and pathological processes, with their occurrence and secretion being strictly regulated by the mechanical microenvironment. Recent studies have confirmed that alterations in the mechanical microenvironment are present in cardiovascular diseases, and the components of EVs can respond to changes in mechanical signals, thereby impacting the progression of these diseases. Additionally, engineered EVs, created by leveraging mechanical microenvironments, can serve as natural drug-delivery vehicles for treating and managing specific diseases. This article systematically reviews the regulatory mechanisms through which the mechanical microenvironment influences EVs and summarizes the role and advancements of EVs derived from this environment in the context of cardiovascular diseases.
Alginate-gelatin hydrogel promotes the neurogenic differentiation potential of bone marrow CD117 hematopoietic stem cells
Peng J
People still hold the concept of using cell-based treatments to regenerate missing neurons in high esteem. CD117 cells are considered favorable stem cells for regenerative medicine. The objective of this research was to examine the impact of Alginate-Gelatin (Alg-Gel) hydrogel on the process of neurogenic differentiation of CD117 cells utilizing a cytokines secretion test conducted in a laboratory setting. To achieve this objective, bone marrow-CD117 cells were isolated using the MACS technique and then transformed into neuron cells using a neurogenic differentiation medium. The characterization of enriched CD117 cells has been done with flow cytometry as well as immunocytochemistry. Next, the cells underwent western blotting assay to evaluate the signaling pathways. Subsequently, the culture media was obtained from both groups in order to determine cytokine levels. The study revealed that the Alg-Gel hydrogel had a notable impact on enhancing the protein expression of neuron markers such as β-tubulin and Wnt/catenin signaling pathway components in CD117 neurogenic differentiated cells. Furthermore, the cultured medium from the experimental group exhibited a notable abundance of IL-6 and IL-10 in comparison to the control group. The observed effects of Alg-Gel hydrogel on neurogenic differentiation of CD117 cells are likely to be caused by the cytokines that are released.
Exosomes derived from epidermal growth factor-like domain protein 6-preconditioned mesenchymal stem cells for diabetic wound healing
Gong C, Xia C and Liu L
Diabetic wounds are difficult to repair effectively in the clinic. Tissue engineering based on mesenchymal stem cells (MSCs) showed great therapeutic potential in wound healing. MSCs-derived exosome could reproduce the effect of MSCs by transferring the bioactive substance to the recipient cells. The biological function of exosomes was determined by the state of the derived MSCs. In this study, we cultured hUC-MSCs with EGFL6 and isolated EGFL6-preconditioned exosomes (EGF-Exos), and then investigated the effect of EGF-Exos on wound healing. The results revealed that EGF-Exos promoted the proliferation and migration of HUVECs, had the anti-inflammtory function and improved angiogenesis. Moreover, we fabricated Gelama hydrogel to load EGF-Exos to repair diabetic wounds. results showed that EGF-Exos contributed to the repair of diabetic wound and provided valuable data for understanding the role of EGF-Exos in diabetic wound healing.
Platelet-rich plasma-derived extracellular vesicles improve liver cirrhosis in mice
Maeda Y, Watanabe Y, Ishikawa N, Yoshida T, Kimura N, Abe H, Sakamaki A, Kamimura H, Yokoo T, Kamimura K, Tsuchiya A and Terai S
Cirrhosis remains a significant clinical challenge due to its poor prognosis and limited treatment options, creating a high unmet medical need for the development of novel therapies. In this study, we analyzed the effects of a novel approach to treat cirrhosis using platelet-rich plasma-derived extracellular vesicles (PRPEV) in mice.
Promising nanotherapeutics of stem cell extracellular vesicles in liver regeneration
Guo N, Wang Y, Wen Z and Fan X
Extracellular vesicles (EVs) have gainedsignificant attention due totheir crucialroles invarious biological systems. This review aims to explore the functions of EVs in both in physiological and pathological states of the liver, with a specific focus on the potential mechanisms and concrete evidence of EVs in liver regeneration processes. The review begins by emphasizing the importance of EVs in maintaining liver health and their involvement in different pathological conditions, starting from the liver's own EVs. Reviewing the role of EVs in liver diseases to reveal the impact of EVs in pathological processes (e.g., hepatitis, liver fibrosis, and cirrhosis) and elucidate their signaling functions at the molecular level. Subsequently, the work concentrates on the functions of EVs in liver regeneration, revealing their key role in repair and regeneration following liver injury by carrying growth factors, nucleic acids, and other bioactive molecules. This part not only theoretically clarifies the mechanisms of EVs in liver regeneration but also experimentally demonstrates their role in promoting liver cell proliferation, inhibiting apoptosis, regulating immune responses, and fostering angiogenesis, laying the groundwork for future clinical applications. Moreover, this work provides a comprehensive analysis of the challenges faced by existing EV-based therapies in liver regeneration and offers prospects for future research directions. It highlights that despite the tremendous potential of EVs in treating liver diseases, there are still technical challenges (e.g., EV isolation and purification, dosage control, and targeted delivery). To overcome these challenges, the review suggests improvements to current technologies and the development of new methods to realize the clinical application of EVs in treating liver diseases.
Orexin-A increases the differentiation of human olfactory sensory neurons through orexin receptor type 1
Chen YT, Young TH, Wang YH, Huang CH, Gao YY and Huang TW
Sensorineural olfactory dysfunction significantly impairs the life quality of patients but without effective treatments to date. Orexin is a neurotrophic factor activates neuronal network activity. However, it is still unknown whether orexin can promote differentiation in human olfactory sensory neurons (OSNs). This study seeks to explore the impact of orexin on the differentiation of human olfactory neuroepithelial cells (HONCs).
Reprogramming canine cryopreserved hepatocytes to hepatic progenitor cells using small molecule compounds
Yamazaki Y, Kikuchi K, Yamada Y, Neo S, Nitta S, Igarashi H, Kamiya A and Hisasue M
Exploring techniques for differentiating and culturing canine hepatocytes serves as a means to establish systems for liver transplantation and drug metabolism testing. However, establishing consistent methods for culturing stable hepatocytes remains a challenge. Recently, several investigations have shown the reprogramming of mature hepatocytes into hepatic progenitor cells by applying specific small molecule compounds, including Y-27632, (a ROCK inhibitor), A-83-01 (a TGFβ inhibitor), and CHIR99021 (a GSK3 inhibitor) (termed YAC) in rat, mouse, and humans, respectively. However, reports or evidence of successful reprogramming using these small-molecule compounds in dogs are absent. This study aimed to induce the differentiation of mature canine hepatocytes into progenitor cells.
A scientometric and visualization analysis of 3D printing scaffolds for vascularized bone tissue engineering over the last decade
Cao S, Wei Y, Yue Y, Wang D, Xiong A, Yang J and Zeng H
The introduction of three-dimensional (3D) printing scaffolds has emerged as an effective approach to achieving satisfactory revascularization for bone tissue engineering (BTE). However, there is a notable absence of analytical and descriptive investigations concerning the trajectory, essential research directions, current research scenario, pivotal investigative focuses, and forthcoming perspectives. Hence, the objective of this research is to offer a thorough overview of the advancements achieved in 3D printing structures for vascularized BTE within the last 10 years. Information extracted from the Web of Science repository spans from January 1, 2014, to April 1, 2024. Utilizing advanced analytical instruments, we conducted comprehensive scientometric and visual analyses. The findings underscore the predominant influence of China, representing 59.62 % of the overall publications and playing a pivotal role in shaping research within this field. Notable productivity was evident at various institutions, including Shanghai Jiao Tong University, Chinese Academy of Sciences, and Sichuan University. Wang Jinwu and Wu Chengtie stand out as the most prolific contributors in this domain. The highest number of publications in this area was contributed by the journal . In this study, osteogenesis imperfecta, osteosarcoma, fractures, osteonecrosis, and cartilage diseases were identified as the most significant disorders investigated in this research area. By providing a comprehensive scientometric assessment, this study benefits both experienced researchers and newcomers alike, offering prompt access to essential information and fostering the extraction of innovative concepts within this specific field.
In situ forming Hydrogel with adding ZnO Nano-particle for effectively methicillin-resistant Staphylococcus aureus infected frostbite injury
Xu X, Wang J, Sun TC, Li Q and Ning RD
Hydrogel has emerged as a promising wound dressing material, and in situ forming hydrogel has emerged as a promising wound dressing recently. But most in situ forming hydrogel are normally unstable. Herein, we report an in-situ forming hydrogel synthesized from poly(Nisopropylacrylamide166---butyl acrylate9)-poly(ethyleneglycol)-poly(N-isopropylacrylamide166---butyl acrylate9) copolymer (P(NIPAM166--nBA9)-PEG-P(NIPAM166-conBA9), denoted as PEP) and zinc oxide nano-particle(ZnO nano-particle) in response to skin temperature. This thermoresponsive hydrogel exhibits sol-gel reversibility at high temperatures, which is closed to the temperature of human skin. To investigate its healing effects, we used the Hydrogel dressing® in an SD rat model. The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus(MRSA) of this PEP-ZnO hydrogel wound dressing are confirmed in vitro and in vivo, which could transparently promote the healing of a MRSA-infected frostbitten skin Injury.
Facile fabrication of chitosan/hyaluronic acid hydrogel-based wound closure material Co-loaded with gold nanoparticles and fibroblast growth factor to improve anti-microbial and healing efficiency in diabetic wound healing and nursing care
Liu X, Peng S, Pei Y, Huo Y, Zong Y, Ren J and Zhao J
Generally, diabetic wounds heal very slowly and inefficiently with an increasing risk of infections. Recent nanotechnology and biomaterial advances elaborate developed multi-functional hydrogels and nanoparticles offer promising solutions to accelerate wound healing for diabetic patients. This research work demonstrates to use of solvent diffusion method to develop hydrogel nanocomposites composed of chitosan (CS), hyaluronic acid (HA), gold (Au), and fibroblast growth factors (FGF). The biological analysis of nanocomposites exhibited enhanced wound healing efficiency by incorporating bioactive molecules like FGF and bioactive Au nanoparticles. cell compatibility analysis (MTT assay) of prepared hydrogel nanocomposites was studied on fibroblast cell lines NIH-3T3-L1 and L929 and exhibited greater cell survival ability (>90 %), cell proliferation and migration ability, which demonstrated the suitability of nanocomposite for wound healing treatment. anti-bacterial analyses established that FGF-Au@CS/HA has strong antibacterial effectiveness against gram-positive and gram-negative pathogens. The observation of the present research revealed that prepared FGF-Au@CS/HA hydrogel composites could be a suitable biomaterial for diabetic wound care, potentially improving its antibacterial and healing efficacies.
Spatial heterogeneity analysis of seeding of human induced pluripotent stem cells for neuroectodermal differentiation
Qatan AAI, Tanbara S, Inamori M, Fukumori K and Kino-Oka M
Preparing a uniform cell population in high-density seeding of adherent human induced pluripotent stem cells (hiPSC) requires stable culture conditions and consistent culture operation. In this study, we evaluated cell distribution patterns by changing cell seeding operations and their impact on differentiation toward the neuroectodermal lineage.
Autologous fat grafting for postoperative breast reconstruction: A systemic review
Yu W, Wang Z, Dai Y, Zhao S, Chen H, Wang S and Xie H
Autologous fat grafting technology has become a new method for breast reconstruction after breast surgery due to its advantages of simple operation, low immunogenicity, fewer complications, high patient acceptance, and natural filling effect. However, the unpredictable fate of transplanted fat limits its widespread application. Currently, many studies have made certain progress in improving the survival rate of fat grafts. This article provides an overview of autologous fat grafting technology, including the mechanisms of fat graft survival, techniques for obtaining and transplanting adipose tissue, methods for enhancing graft survival, and complications associated with fat grafting.
Extracellular vesicle mimetics engineered from mesenchymal stem cells and curcumin promote fibrosis regression in a mouse model of thioacetamide-induced liver fibrosis
Gopal A, Gangadaran P, Rajendran RL, Oh JM, Lee HW, Hong CM, Kalimuthu S, Han MH, Lee J and Ahn BC
Recent research suggests that advanced liver fibrosis could be reversed, but the therapeutic agents needed for the prevention of liver fibrosis remain to be elucidated. The beneficial effects of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) on liver fibrosis have been reported. However, the large-scale production of MSC-EVs remains challenging. The present study investigated the therapeutic effects of mouse MSC-derived EV mimetics (MEVMs) in combination with curcumin (antifibrotic compound) using a mouse model of thioacetamide-induced liver fibrosis. MEVMs were prepared through the serial extrusion of MSCs. These MEVMs were similar in size and morphology to the EVs. The biodistribution study showed that fluorescently labeled MEVMs predominantly accumulated in the liver. The establishment of liver fibrosis was confirmed via increased collagen (histology), liver fibrosis score, α-smooth muscle actin (α-SMA), and vimentin proteins levels. Treatment with MEVMs, curcumin, or their combination decreased the amount of collagen in liver tissues, with the antifibrotic effects of MEVMs being further confirmed by the liver fibrosis score. All treatments decreased the expression of , α-SMA, and vimentin. MEVMs showed superior effects than curcumin. Thus, MSC-derived EVMs could be a potential alternative for the treatment of liver fibrosis.
Unveiling the superior function of RADA in bone regeneration compared to KSL as two critical cores within self-assembling peptide nanofibers: Insights from in vitro and in vivo studies
Rasoulian B, Sheikholislam Z, Houshdar Tehrani MH, Chegeni S, Hoveizi E, Rezayat SM and Tavakol S
Self-assembling peptide nanofibers have emerged as promising biomaterials in the realm of bone tissue engineering due to their biocompatibility, biodegradability, and ability to mimic the native extracellular matrix. This study delved into the comparative efficacy of two distinct self-assembling peptide nanofibers, RADA-BMHP1 and KSL-BMHP1, both incorporating the biological motif of BMHP1, but differing in their core peptide sequences.
Regenerative medicine in cardiovascular disease
Goto T, Nakamura Y, Ito Y and Miyagawa S
Owing to the rapid increase in the number of people with severe heart failure, regenerative medicine is anticipated to play a role in overcoming the limitations inherent in existing surgical interventions. There are essentially two types of cardiac regenerative therapies for a failing heart. Cellular regenerative therapies using various stem cells improve the functional recovery of the heart mainly by cytokine paracrine effects. The implantation of induced pluripotent stem cell-derived cardiomyocytes can contribute not only to the inhibition of adverse heart remodeling by paracrine effects but also to the supply of newly born functional myocytes with the recipient myocardium as "mechanically working cells." Cell transplantation, including autologous myoblast transplantation, reduces heart failure exacerbations and benefits patients without the need for other treatment options. Although cellular therapy is currently the mainstream approach, it requires an in-house cell-processing center with an aseptic environment. In addition, these stem cells are usually introduced via several invasive delivery methods, including intracoronary administration, and cellular sheet implantation. Simplifying the culture methods for these cells is a crucial problem that needs to be resolved. Drug-induced regenerative therapy is another option that enhances self-endogenous regenerative systems in the human body and does not require invasive methods or cell cultures. Therefore, drug-induced regenerative therapies may overcome the disadvantages of these cellular therapies. The purpose of this report is to summarize cell transplantation therapy in the cardiovascular system and regenerative therapy for heart failure using an autologous endogenous regenerative system.
Mesenchymal stem cells: Guardians of women's health
Gao G, Li L, Li C, Liu D, Wang Y and Li C
Mesenchymal stem cells (MSCs) have attracted more and more attention because of their multidirectional differentiation potential, immune regulatory abilities and self-renewal capacity. In recent years, their use has become prominent in the domains of regenerative medicine and tissue engineering. MSCs have shown promise in therapeutic studies for a variety of diseases and have become a new source of innovative solutions for the treatment of some obstetric and gynecological diseases. This review systematically presents the latest research on the use of MSCs in the treatment of obstetrics- and gynecology-related diseases. Specifically, this review encompasses the latest findings related to the role of MSCs in premature ovarian failure, polycystic ovary syndrome, ovarian cancer, fallopian tube-related diseases, uterine adhesions, endometriosis, cesarean scar defects, postmenopausal osteoporosis, and pelvic floor dysfunction. The shortcomings and challenges of the future use of MSCs in disease treatment are also discussed, with the intent to motivate improvements in MSC applications in clinical therapy. It is believed that with further research, MSCs will play a more important role in the treatment of obstetrics- and gynecology-related diseases.