Reetta Sartoneva, Kaarlo Paakinaho, Markus Hannula, Kirsi Kuismanen, Heini Huhtala, Jari Hyttinen, Susanna Miettinen
{"title":"Ascorbic Acid 2-Phosphate Releasing Supercritically Foamed Porous Poly-L-Lactide-Co-ε-Caprolactone Scaffold Enhances the Collagen Production of Human Vaginal Stromal Cells: A New Approach for Vaginal Tissue Engineering.","authors":"Reetta Sartoneva, Kaarlo Paakinaho, Markus Hannula, Kirsi Kuismanen, Heini Huhtala, Jari Hyttinen, Susanna Miettinen","doi":"10.1007/s13770-023-00603-3","DOIUrl":"10.1007/s13770-023-00603-3","url":null,"abstract":"<p><strong>Background: </strong>The reconstructive surgery of vaginal defects is highly demanding and susceptible to complications, especially in larger defects requiring nonvaginal tissue grafts. Thus, tissue engineering-based solutions could provide a potential approach to the reconstruction of vaginal defects.</p><p><strong>Methods: </strong>Here, we evaluated a novel porous ascorbic acid 2-phosphate (A2P)-releasing supercritical carbon dioxide foamed poly-L-lactide-co-ε-caprolactone (scPLCL<sub>A2P</sub>) scaffold for vaginal reconstruction with vaginal epithelial (EC) and stromal (SC) cells. The viability, proliferation, and phenotype of ECs and SCs were evaluated in monocultures and in cocultures on d 1, d 7 and d 14. Furthermore, the collagen production of SCs on scPLCL<sub>A2P</sub> was compared to that on scPLCL without A2P on d 14.</p><p><strong>Results: </strong>Both ECs and SCs maintained their viability on the scPLCL<sub>A2P</sub> scaffold in mono- and coculture conditions, and the cells maintained their typical morphology during the 14-d culture period. Most importantly, the scPLCL<sub>A2P</sub> scaffolds supported the collagen production of SCs superior to plain scPLCL based on total collagen amount, collagen I and III gene expression results and collagen immunostaining results.</p><p><strong>Conclusion: </strong>This is the first study evaluating the effect of A2P on vaginal tissue engineering, and the results are highly encouraging, indicating that scPLCL<sub>A2P</sub> has potential as a scaffold for vaginal tissue engineering.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"81-96"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transplantation of Gelatin Microspheres Loaded with Wharton's Jelly Derived Mesenchymal Stem Cells Facilitates Cartilage Repair in Mice.","authors":"Xiaolin Chen, Sunxing Huang, Yongxia Niu, Mingxun Luo, Haiying Liu, Yiren Jiao, Junjiu Huang","doi":"10.1007/s13770-023-00574-5","DOIUrl":"10.1007/s13770-023-00574-5","url":null,"abstract":"<p><strong>Background: </strong>Knee osteoarthritis (KOA) is a prevalent chronic joint disease caused by various factors. Mesenchymal stem cells (MSCs) therapy is an increasingly promising therapeutic option for osteoarthritis. However, the chronic inflammation of knee joint can severely impede the therapeutic effects of transplanted cells. Gelatin microspheres (GMs) are degradable biomaterial that have various porosities for cell adhesion and cell-cell interaction. Excellent elasticity and deformability of GMs make it an excellent injectable vehicle for cell delivery.</p><p><strong>Methods: </strong>We created Wharton's jelly derived mesenchymal stem cells (WJMSCs)-GMs complexes and assessed the effects of GMs on cell activity, proliferation and chondrogenesis. Then, WJMSCs loaded in GMs were transplanted in the joint of osteoarthritis mice. After four weeks, joint tissue was collected for histological analysis. Overexpressing-luciferase WJMSCs were performed to explore cell retention in mice.</p><p><strong>Results: </strong>In vitro experiments demonstrated that WJMSCs loaded with GMs maintained cell viability and proliferative potential. Moreover, GMs enhanced the chondrogenesis differentiation of WJMSCs while alleviated cell hypertrophy. In KOA mice model, transplantation of WJMSCs-GMs complexes promoted cartilage regeneration and cartilage matrix formation, contributing to the treatment of KOA. Compared with other groups, in WJMSCs+GMs group, there were fewer cartilage defects and with a more integrated tibia structure. Tracking results of stable-overexpressing luciferase WJMSCs demonstrated that GMs significantly extended the retention time of WJMSCs in knee joint cavity.</p><p><strong>Conclusion: </strong>Our results indicated that GMs facilitate WJMSCs mediated knee osteoarthritis healing in mice by promoting cartilage regeneration and prolonging cell retention. It might potentially provide an optimal strategy for the biomaterial-stem cell based therapy for knee osteoarthritis.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"171-183"},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zifei Shao, Jinhao Xu, Xiaoyang Xu, Xiang Wang, Yuxi Zhou, Yiyang Li, Kun Li
{"title":"Exosomes Derived from Human Adipose Mesenchymal Stem Cells Inhibits Fibrosis and Treats Oral Submucous Fibrosis via the miR-181a-5p/Smad2 Axis.","authors":"Zifei Shao, Jinhao Xu, Xiaoyang Xu, Xiang Wang, Yuxi Zhou, Yiyang Li, Kun Li","doi":"10.1007/s13770-023-00579-0","DOIUrl":"10.1007/s13770-023-00579-0","url":null,"abstract":"<p><strong>Background: </strong>Oral submucous fibrosis (OSF) is a chronic disease with carcinogenic tendency that poses a non-negligible threat to human health. Exosomes derived from human adipose mesenchymal stem cells (ADSC-Exo) reduces visceral and cutaneous fibroses, but their role in OSF has received little attention. The aim of this study was to investigate the effects of ADSC-Exo on OSF and elucidate the mechanism.</p><p><strong>Methods: </strong>In brief, ADSCs were extracted from adipose tissues and subjected to flow cytometry and induction culture. Fibroblasts were isolated from human buccal mucosa and subjected to immunofluorescence. Myofibroblasts were obtained from fibroblasts induced by arecoline and identified. Immunofluorescence assay confirmed that myofibroblasts could take up ADSC-Exo. The effects of ADSC-Exo on the proliferative and migratory capacities of myofibroblasts were examined using the Cell Counting Kit-8 and scratch assay. Real-time quantitative polymerase chain reaction (qPCR) was performed to evaluate mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad7, collagen type 1 (Col1), Col3, alpha smooth muscle actin (α-SMA), fibronectin, and vimentin. Western blotting was performed to detect phospho (p)-Smad2, Smad2, p-Smad2/3, Smad2/3, Smad7, Col1, Col3, α-SMA, fibronectin, and vimentin. Furthermore, the dual-luciferase reporter assay was performed to prove that miR-181a-5p in ADSC-Exo directly inhibited the expression of Smad2 mRNA to regulate the transforming growth factor beta (TGF-β) pathway. We also performed qPCR and western blotting to verify the results.</p><p><strong>Results: </strong>ADSC-Exo could promote the proliferation and migration of myofibroblasts, reduce the expressions of p-smad2, Smad2, p-smad2/3, Smad2/3, Col1, αSMA, fibronectin, and vimentin and elevated the levels of Smad7 and Col3. In addition, miR-181a-5p was highly expressed in ADSC-Exo and bound to the 3'-untranslated region of Smad2. ADSC-Exo enriched with miR-181a-5p reduced collagen production in myofibroblasts and modulated the TGF-β pathway.</p><p><strong>Conclusions: </strong>ADSC-Exo promoted the proliferative and migratory capacities of myofibroblasts and inhibited collagen deposition and trans-differentiation of myofibroblasts in vitro. miR-181a-5p in exosomes targets Smad2 to regulate the TGF-β pathway in myofibroblasts. ADSC-Exo perform antifibrotic actions through the miR-181a-5p/Smad2 axis and may be a promising clinical treatment for OSF.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"123-135"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melis Asal, Mila Rep, Hetty J. Bontkes, Sandra J. van Vliet, Reina E. Mebius, Susan Gibbs
{"title":"Towards Full Thickness Small Intestinal Models: Incorporation of Stromal Cells","authors":"Melis Asal, Mila Rep, Hetty J. Bontkes, Sandra J. van Vliet, Reina E. Mebius, Susan Gibbs","doi":"10.1007/s13770-023-00600-6","DOIUrl":"https://doi.org/10.1007/s13770-023-00600-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Since small intestine is one of the major barriers of the human body, there is a need to develop reliable in vitro human small intestinal models. These models should incorporate both the epithelial and lamina propria compartments and have similar barrier properties compared to that of the human tissue. These properties are essential for various applications, such as studying cell–cell interaction, intestinal diseases and testing permeability and metabolism of drugs and other compounds. The small intestinal lamina propria contains multiple stromal cell populations with several important functions, such as secretion of extracellular matrix proteins and soluble mediators. In addition, stromal cells influence the intestinal epithelial barrier, support the intestinal stem cell niche and interact with immune cells.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this review, we provide an extensive overview on the different types of lamina propria stromal cells found in small intestine and describe a combination of molecular markers that can be used to distinguish each different stromal cell type. We focus on studies that incorporated stromal cells into human representative small intestine models cultured on transwells.</p><h3 data-test=\"abstract-sub-heading\">Results and Conclusion</h3><p>These models display enhanced epithelial morphology, increased cell proliferation and human-like barrier properties, such as low transepithelial electrical resistance (TEER) and intermediate permeability, thus better mimicking the native human small intestine than models only consisting of an epithelium which generally show high TEER and low permeability.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":"76 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138744081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew I. Morrison, Aleksandra M. Mikula, Sander W. Spiekstra, Michael de Kok, Alsya J. Affandi, Henk P. Roest, Luc J. W. van der Laan, Charlotte M. de Winde, Jasper J. Koning, Susan Gibbs, Reina E. Mebius
{"title":"An Organotypic Human Lymph Node Model Reveals the Importance of Fibroblastic Reticular Cells for Dendritic Cell Function","authors":"Andrew I. Morrison, Aleksandra M. Mikula, Sander W. Spiekstra, Michael de Kok, Alsya J. Affandi, Henk P. Roest, Luc J. W. van der Laan, Charlotte M. de Winde, Jasper J. Koning, Susan Gibbs, Reina E. Mebius","doi":"10.1007/s13770-023-00609-x","DOIUrl":"https://doi.org/10.1007/s13770-023-00609-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background:</h3><p>Human lymph node (HuLN) models have emerged with invaluable potential for immunological research and therapeutic application given their fundamental role in human health and disease. While fibroblastic reticular cells (FRCs) are instrumental to HuLN functioning, their inclusion and recognition of importance for organotypic <i>in vitro</i> lymphoid models remain limited.</p><h3 data-test=\"abstract-sub-heading\">Methods:</h3><p>Here, we established an <i>in vitro</i> three-dimensional (3D) model in a collagen-fibrin hydrogel with primary FRCs and a dendritic cell (DC) cell line (MUTZ-3 DC). To study and characterise the cellular interactions seen in this 3D FRC-DC organotypic model compared to the native HuLN; flow cytometry, immunohistochemistry, immunofluorescence and cytokine/chemokine analysis were performed.</p><h3 data-test=\"abstract-sub-heading\">Results:</h3><p>FRCs were pivotal for survival, proliferation and localisation of MUTZ-3 DCs. Additionally, we found that CD1a expression was absent on MUTZ-3 DCs that developed in the presence of FRCs during cytokine-induced MUTZ-3 DC differentiation, which was also seen with primary monocyte-derived DCs (moDCs). This phenotype resembled HuLN-resident DCs, which we detected in primary HuLNs, and these CD1a<sup>−</sup> MUTZ-3 DCs induced T cell proliferation within a mixed leukocyte reaction (MLR), indicating a functional DC status. FRCs expressed podoplanin (PDPN), CD90 (Thy-1), CD146 (MCAM) and Gremlin-1, thereby resembling the DC supporting stromal cell subset identified in HuLNs.</p><h3 data-test=\"abstract-sub-heading\">Conclusion:</h3><p>This 3D FRC-DC organotypic model highlights the influence and importance of FRCs for DC functioning in a more realistic HuLN microenvironment. As such, this work provides a starting point for the development of an <i>in vitro</i> HuLN.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":"7 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138744138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soo Jin Park, Yoon Young Kim, Wonhyoung Park, Sunwoo Park, Ji Yeon Han, Sung Woo Kim, Hoon Kim, Seung-Yup Ku
{"title":"Effects of Cetrorelix on Ovary and Endometrium Prior to Anti-PD-L1 Antibody in Murine Model","authors":"Soo Jin Park, Yoon Young Kim, Wonhyoung Park, Sunwoo Park, Ji Yeon Han, Sung Woo Kim, Hoon Kim, Seung-Yup Ku","doi":"10.1007/s13770-023-00617-x","DOIUrl":"https://doi.org/10.1007/s13770-023-00617-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background:</h3><p>Recent anti-cancer agents, immune checkpoint inhibitors (ICIs), have emerged as effective agents targeting the programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. While the administration of gonadotropin-releasing hormone (GnRH) analogs before cytotoxic agents is known to preserve female reproductive organ function, the potential effects of ICIs and the protective impact of GnRH analogs on female reproductive organs, especially concerning ovarian reserve and endometrial receptivity, remain unknown. In this study, we attempted to elucidate the protective or regenerative effect on the female reproductive organ of cetrorelix prior to anti-PD-L1 antibody administration.</p><h3 data-test=\"abstract-sub-heading\">Method:</h3><p>Using a murine model, we examined the effects of Anti-PD-L1 antibody treatment on ovarian and uterine morphology, compared them with controls, and further assessed any potential protective effect of cetrorelix, a GnRH analog. Histological examinations and quantitative reverse transcription polymerase chain reaction were employed to study the morphological changes and associated gene expression patterns.</p><h3 data-test=\"abstract-sub-heading\">Results:</h3><p>Anti-PD-L1 treatment led to a significant depletion of primordial/primary ovarian follicles and impaired decidualization in uterine stromal cells. However, while pretreatment with cetrorelix could restore normal decidualization patterns in the uterus, it did not significantly ameliorate ovarian follicular reductions. Gene expression analysis reflected these observations, particularly with marked changes in the expression of key genes like <i>Prl</i> and <i>Igfbp1</i>, pivotal in uterine decidualization.</p><h3 data-test=\"abstract-sub-heading\">Conclusion:</h3><p>Our study underscores the potential reproductive implications of cetrorelix treatment prior to Anti-PD-L1 therapy, shedding light on its short-term protective effects on the uterus. Further studies are necessary to understand long-term and clinical implications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":"22 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138685062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bhavani Gopalakrishnan, Uri Galili, August Dunbar, Luis Solorio, Riyi Shi, Jianming Li
{"title":"α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State","authors":"Bhavani Gopalakrishnan, Uri Galili, August Dunbar, Luis Solorio, Riyi Shi, Jianming Li","doi":"10.1007/s13770-023-00613-1","DOIUrl":"https://doi.org/10.1007/s13770-023-00613-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background:</h3><p>Macrophages and microglia play critical roles after spinal cord injury (SCI), with the pro-healing, anti-inflammatory (M2) subtype being implicated in tissue repair. We hypothesize that promoting this phenotype within the post-injured cord microenvironment may provide beneficial effects for mitigating tissue damage. As a proof of concept, we propose the use of nanoparticles incorporating the carbohydrate antigen, galactose-α-1,3-galactose (α-gal epitope) as an immunomodulator to transition human microglia (HMC3) cells toward a pro-healing state.</p><h3 data-test=\"abstract-sub-heading\">Methods:</h3><p>Quiescent HMC3 cells were acutely exposed to α-gal nanoparticles in the presence of human serum and subsequently characterized for changes in cell shape, expression of anti or pro-inflammatory markers, and secretion of phenotype-specific cytokines.</p><h3 data-test=\"abstract-sub-heading\">Results:</h3><p>HMC3 cells treated with serum activated α-gal nanoparticles exhibited rapid enlargement and shape change in addition to expressing CD68. Moreover, these activated cells showed increased expression of anti-inflammatory markers like Arginase-1 and CD206 without increasing production of pro-inflammatory cytokines TNF-α or IL-6.</p><h3 data-test=\"abstract-sub-heading\">Conclusion:</h3><p>This study is the first to show that resting human microglia exposed to a complex of α-gal nanoparticles and anti-Gal (from human serum) can be activated and polarized toward a putative M2 state. The data suggests that α-gal nanoparticles may have therapeutic relevance to the CNS microenvironment, in both recruiting and polarizing macrophages/microglia at the application site. The immunomodulatory activity of these α-gal nanoparticles post-SCI is further described in the companion work (Part II).</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3><p>Resting microglia subjected to α-gal nanoparticle treatment in the presence of anti-Gal (found in serum) become activated and exhibit pro-healing phenotypic markers (Arginase-1, CD206) and secrete VEGF. Expression of pro-inflammatory markers (IL-6, TNF-α) was concomitantly reduced.</p>\u0000","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":"5 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138685063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hye-Jeong Jang, Kyu-Sik Shim, Jinah Lee, Joo Hyeon Park, Seong-Jun Kang, Young Min Shin, Jung Bok Lee, Wooyeol Baek, Jeong-Kee Yoon
{"title":"Engineering of Cell Derived-Nanovesicle as an Alternative to Exosome Therapy","authors":"Hye-Jeong Jang, Kyu-Sik Shim, Jinah Lee, Joo Hyeon Park, Seong-Jun Kang, Young Min Shin, Jung Bok Lee, Wooyeol Baek, Jeong-Kee Yoon","doi":"10.1007/s13770-023-00610-4","DOIUrl":"https://doi.org/10.1007/s13770-023-00610-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Exosomes, nano-sized vesicles ranging between 30 and 150 nm secreted by human cells, play a pivotal role in long-range intercellular communication and have attracted significant attention in the field of regenerative medicine. Nevertheless, their limited productivity and cost-effectiveness pose challenges for clinical applications. These issues have recently been addressed by cell-derived nanovesicles (CDNs), which are physically synthesized exosome-mimetic nanovesicles from parent cells, as a promising alternative to exosomes. CDNs exhibit structural, physical, and biological properties similar to exosomes, containing intracellular protein and genetic components encapsulated by the cell plasma membrane. These characteristics allow CDNs to be used as regenerative medicine and therapeutics on their own, or as a drug delivery system.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The paper reviews diverse methods for CDN synthesis, current analysis techniques, and presents engineering strategies to improve lesion targeting efficiency and/or therapeutic efficacy.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>CDNs, with their properties similar to those of exosomes, offer a cost-effective and highly productive alternative due to their non-living biomaterial nature, nano-size, and readiness for use, allowing them to overcome several limitations of conventional cell therapy methods.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Ongoing research and enhancement of CDNs engineering, along with comprehensive safety assessments and stability analysis, exhibit vast potential to advance regenerative medicine by enabling the development of efficient therapeutic interventions.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138561986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alejandro Reina-Mahecha, Martine J Beers, Hugo C van der Veen, Inge S Zuhorn, Theo G van Kooten, Prashant K Sharma
{"title":"A Review of the Role of Bioreactors for iPSCs-Based Tissue-Engineered Articular Cartilage.","authors":"Alejandro Reina-Mahecha, Martine J Beers, Hugo C van der Veen, Inge S Zuhorn, Theo G van Kooten, Prashant K Sharma","doi":"10.1007/s13770-023-00573-6","DOIUrl":"10.1007/s13770-023-00573-6","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is the most common degenerative joint disease without an ultimate treatment. In a search for novel approaches, tissue engineering (TE) has shown great potential to be an effective way for hyaline cartilage regeneration and repair in advanced stages of OA. Recently, induced pluripotent stem cells (iPSCs) have been appointed to be essential stem cells for degenerative disease treatment because they allow a personalized medicine approach. For clinical translation, bioreactors in combination with iPSCs-engineerd cartilage could match patients needs, serve as platform for large-scale patient specific cartilage production, and be a tool for patient OA modelling and drug screening. Furthermore, to minimize in vivo experiments and improve cell differentiation and cartilage extracellular matrix (ECM) deposition, TE combines existing approaches with bioreactors.</p><p><strong>Methods: </strong>This review summarizes the current understanding of bioreactors and the necessary parameters when they are intended for cartilage TE, focusing on the potential use of iPSCs.</p><p><strong>Results: </strong>Bioreactors intended for cartilage TE must resemble the joint cavity niche. However, recreating human synovial joints is not trivial because the interactions between various stimuli are not entirely understood.</p><p><strong>Conclusion: </strong>The use of mechanical and electrical stimulation to differentiate iPSCs, and maintain and test chondrocytes are key stimuli influencing hyaline cartilage homeostasis. Incorporating these stimuli to bioreactors can positively impact cartilage TE approaches and their possibility for posterior translation into the clinics.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1041-1052"},"PeriodicalIF":3.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sohee Park, Yeuni Yu, Gi Cheol Park, Sung-Chan Shin, Ji Min Kim, Byung-Joo Lee, Yun Hak Kim
{"title":"Proliferation-Related Features of the Human Mesenchymal Stem Cells Derived from Palatine Tonsils, Adipose Tissues, and Bone Marrow.","authors":"Sohee Park, Yeuni Yu, Gi Cheol Park, Sung-Chan Shin, Ji Min Kim, Byung-Joo Lee, Yun Hak Kim","doi":"10.1007/s13770-023-00564-7","DOIUrl":"10.1007/s13770-023-00564-7","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are widely used in regenerative medicine and cell-based transplantations. However, an in-depth comparison of the different MSC origins is lacking. This study aimed to compare the expression of adipose-derived (AMSCs), bone marrow-derived (BMSCs), and tonsil-derived (TMSCs) and evaluate whether TMSCs are good alternatives for AMSCs or BMSCs.</p><p><strong>Methods: </strong>We analyzed the expression levels of 47,000 transcripts in AMSCs (n = 4), BMSCs (n = 4), and TMSCs (n = 4) using GeneChip. Microarray data were analyzed using the LIMMA package to compare the TMSCs, AMSCs, and BMSCs. Hub genes were analyzed using STRING and Cytoscape. To ascertain the functional roles of AURKA and AURKB, small interfering RNA (siRNA) molecules specifically targeting AURKA and AURKB mRNA were synthesized and employed to induce knockdown of AURKA and AURKB in TMSC and AMSC. We analyzed the expression level of OCT4, SOX-2, and NANOG genes in TMSC and AMSCs by cell culture and real-time PCR.</p><p><strong>Results: </strong>We identified commonly increased 256 and decreased 160 genes in TMSCs from the differentially expressed genes (DEGs) between the TMSCs, AMSCs, and BMSCs. In the DEG-based protein-protein interaction and gene set enrichment analysis, hub genes (AURKA, AURKB, CDC20, and BUB1) highly expressed in TMSCs were enriched for development- and progression-related oocyte meiosis, the cell cycle, and ubiquitin-mediated proteolysis. In vitro analysis demonstrated that cells with downregulated expression of AURKA and AURKB exhibited a significant reduction in proliferation compared to control cells. However, silencing of the genes did not affect the differentiation capacity in TMSCs and AMSCs.</p><p><strong>Conclusion: </strong>Our study compared MSCs of different origins to better understand the similarities and differences among these cell types.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1119-1132"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10375196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}