Cells

Research

17 pages, 11640 KiB

Open AccessArticle

Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner

by Livia Provitera, Andrea Tomaselli, Genny Raffaeli, Stefania Crippa, Cristina Arribas, Ilaria Amodeo, Silvia Gulden, Giacomo Simeone Amelio, Valeria Cortesi, Francesca Manzoni, Gaia Cervellini, Jacopo Cerasani, Camilla Menis, Nicola Pesenti, Matteo Tripodi, Ludovica Santi, Marco Maggioni, Caterina Lonati, Samanta Oldoni, Francesca Algieri, Felipe Garrido, Maria Ester Bernardo, Fabio Mosca and Giacomo Cavallaro Show full author list Hide full author list

Cells 2023, 12(5), 760; https://doi.org/10.3390/cells12050760 - 27 Feb 2023

Cited by 3 | Viewed by 2104

Abstract

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of [...] Read more.

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3–6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 10⁶ or 1 × 10⁶) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 10⁶) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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16 pages, 1005 KiB

Open AccessArticle

The Composition of Adipose-Derived Regenerative Cells Isolated from Lipoaspirate Using a Point of Care System Does Not Depend on the Subject’s Individual Age, Sex, Body Mass Index and Ethnicity

by Christoph Schmitz, Christopher Alt, Alon R. Azares, David A. Pearce, Tiffany R. Facile, John P. Furia, Nicola Maffulli, Claire Huang and Eckhard U. Alt

Cells 2023, 12(1), 30; https://doi.org/10.3390/cells12010030 - 21 Dec 2022

Cited by 5 | Viewed by 3106

Abstract

Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject’s individual age, sex, body mass index and ethnicity. [...] Read more.

Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject’s individual age, sex, body mass index and ethnicity. UA-ADRCs were isolated from lipoaspirate from n = 232 subjects undergoing elective lipoplasty using the Transpose RT system (InGeneron, Inc.; Houston, TX, USA). The UA-ADRCs were assessed for the number of nucleated cells, cell viability and the number of viable nucleated cells per gram of adipose tissue harvested. Cells from n = 37 subjects were further characterized using four-channel flow cytometry. The present study shows, for the first time, that key characteristics of UA-ADRCs can be independent of the subject’s age, sex, BMI and ethnicity. This result has important implications for the general applicability of UA-ADRCs in regeneration of musculoskeletal tissue. Future studies must determine whether the independence of key characteristics of UA-ADRCs of the subject’s individual age, sex, BMI and ethnicity only applies to the system used in the present study, or also to others of the more than 25 different experimental methods and commercially available systems used to isolate UA-ADRCs from lipoaspirate that have been described in the literature. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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15 pages, 3809 KiB

Open AccessFeature PaperArticle

Peripheral Nerve Regeneration–Adipose-Tissue-Derived Stem Cells Differentiated by a Three-Step Protocol Promote Neurite Elongation via NGF Secretion

by Silvan Klein, Andreas Siegmund, Andreas Eigenberger, Valerie Hartmann, Felix Langewost, Nicolas Hammer, Alexandra Anker, Konstantin Klein, Christian Morsczeck, Lukas Prantl and Oliver Felthaus

Cells 2022, 11(18), 2887; https://doi.org/10.3390/cells11182887 - 15 Sep 2022

Cited by 3 | Viewed by 2160

Abstract

The lack of supportive Schwann cells in segmental nerve lesions seems to be one cornerstone for the problem of insufficient nerve regeneration. Lately, adipose-tissue-derived stem cells (ASCs) differentiated towards SC (Schwann cell)-like cells seem to fulfill some of the needs for ameliorated nerve [...] Read more.

The lack of supportive Schwann cells in segmental nerve lesions seems to be one cornerstone for the problem of insufficient nerve regeneration. Lately, adipose-tissue-derived stem cells (ASCs) differentiated towards SC (Schwann cell)-like cells seem to fulfill some of the needs for ameliorated nerve recovery. In this study, three differentiation protocols were investigated for their ability to differentiate ASCs from rats into specialized SC phenotypes. The differentiated ASCs (dASCs) were compared for their expressions of neurotrophins (NGF, GDNF, BDNF), myelin markers (MBP, P0), as well as glial-marker proteins (S100, GFAP) by RT-PCR, ELISA, and Western blot. Additionally, the influence of the medium conditioned by dASCs on a neuron-like cell line was evaluated. The dASCs were highly diverse in their expression profiles. One protocol yielded relatively high expression rates of neurotrophins, whereas another protocol induced myelin-marker expression. These results were reproducible when the ASCs were differentiated on surfaces potentially used for nerve guidance conduits. The NGF secretion affected the neurite outgrowth significantly. It remains uncertain what features of these SC-like cells contribute the most to adequate functional recovery during the different phases of nerve recovery. Nevertheless, therapeutic applications should consider these diverse phenotypes as a potential approach for stem-cell-based nerve-injury treatment. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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19 pages, 2266 KiB

Open AccessArticle

Comparison of Muscle Regeneration after BMSC-Conditioned Medium, Syngeneic, or Allogeneic BMSC Injection

by Barbara Świerczek-Lasek, Lukasz Tolak, Lukasz Bijoch, Marzena Stefaniuk, Patrycja Szpak, Ilona Kalaszczynska, Władysława Streminska, Maria A. Ciemerych and Karolina Archacka

Cells 2022, 11(18), 2843; https://doi.org/10.3390/cells11182843 - 12 Sep 2022

Cited by 4 | Viewed by 2143

Abstract

For many years optimal treatment for dysfunctional skeletal muscle characterized, for example, by impaired or limited regeneration, has been searched. Among the crucial factors enabling its development is finding the appropriate source of cells, which could participate in tissue reconstruction or serve as [...] Read more.

For many years optimal treatment for dysfunctional skeletal muscle characterized, for example, by impaired or limited regeneration, has been searched. Among the crucial factors enabling its development is finding the appropriate source of cells, which could participate in tissue reconstruction or serve as an immunomodulating agent (limiting immune response as well as fibrosis, that is, connective tissue formation), after transplantation to regenerating muscles. MSCs, including those derived from bone marrow, are considered for such applications in terms of their immunomodulatory properties, as their naive myogenic potential is rather limited. Injection of autologous (syngeneic) or allogeneic BMSCs has been or is currently being tested and compared in many potential clinical treatments. In the present study, we verified which approach, that is, the transplantation of either syngeneic or allogeneic BMSCs or the injection of BMSC-conditioned medium, would be the most beneficial for skeletal muscle regeneration. To properly assess the influence of the tested treatments on the inflammation, the experiments were carried out using immunocompetent mice, which allowed us to observe immune response. Combined analysis of muscle histology, immune cell infiltration, and levels of selected chemokines, cytokines, and growth factors important for muscle regeneration, showed that muscle injection with BMSC-conditioned medium is the most beneficial strategy, as it resulted in reduced inflammation and fibrosis development, together with enhanced new fiber formation, which may be related to, i.e., elevated level of IGF-1. In contrast, transplantation of allogeneic BMSCs to injured muscles resulted in a visible increase in the immune response, which hindered regeneration by promoting connective tissue formation. In comparison, syngeneic BMSC injection, although not detrimental to muscle regeneration, did not result in such significant improvement as CM injection. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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17 pages, 2954 KiB

Open AccessArticle

Human Adipose Mesenchymal Stromal/Stem Cells Improve Fat Transplantation Performance

by Maria Serena Piccinno, Tiziana Petrachi, Marco Pignatti, Alba Murgia, Giulia Grisendi, Olivia Candini, Elisa Resca, Valentina Bergamini, Francesco Ganzerli, Alberto Portone, Ilenia Mastrolia, Chiara Chiavelli, Ilaria Castelli, Daniela Bernabei, Mara Tagliazucchi, Elisa Bonetti, Francesca Lolli, Giorgio De Santis, Massimo Dominici and Elena Veronesi

Cells 2022, 11(18), 2799; https://doi.org/10.3390/cells11182799 - 7 Sep 2022

Cited by 2 | Viewed by 2222

Abstract

The resorption rate of autologous fat transfer (AFT) is 40–60% of the implanted tissue, requiring new surgical strategies for tissue reconstruction. We previously demonstrated in a rabbit model that AFT may be empowered by adipose-derived mesenchymal stromal/stem cells (AD-MSCs), which improve graft persistence [...] Read more.

The resorption rate of autologous fat transfer (AFT) is 40–60% of the implanted tissue, requiring new surgical strategies for tissue reconstruction. We previously demonstrated in a rabbit model that AFT may be empowered by adipose-derived mesenchymal stromal/stem cells (AD-MSCs), which improve graft persistence by exerting proangiogenic/anti-inflammatory effects. However, their fate after implantation requires more investigation. We report a xenograft model of adipose tissue engineering in which NOD/SCID mice underwent AFT with/without human autologous AD-MSCs and were monitored for 180 days (d). The effect of AD-MSCs on AFT grafting was also monitored by evaluating the expression of CD31 and F4/80 markers. Green fluorescent protein-positive AD-MSCs (AD-MSC-GFP) were detected in fibroblastoid cells 7 days after transplantation and in mature adipocytes at 60 days, indicating both persistence and differentiation of the implanted cells. This evidence also correlated with the persistence of a higher graft weight in AFT-AD-MSC compared to AFT alone treated mice. An observation up to 180 d revealed a lower resorption rate and reduced lipidic cyst formation in the AFT-AD-MSC group, suggesting a long-term action of AD-MSCs in support of AFT performance and an anti-inflammatory/proangiogenic activity. Together, these data indicate the protective role of adipose progenitors in autologous AFT tissue resorption. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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19 pages, 4767 KiB

Open AccessArticle

Differentiation Capacity of Bone Marrow-Derived Rat Mesenchymal Stem Cells from DsRed and Cre Transgenic Cre/loxP Models

by Hsiang-Ching Tseng, Menq-Rong Wu, Chia-Hsun Lee and Jong-Kai Hsiao

Cells 2022, 11(17), 2769; https://doi.org/10.3390/cells11172769 - 5 Sep 2022

Cited by 4 | Viewed by 2367

Abstract

Cre/loxP recombination is a well-established technique increasingly used for modifying DNA both in vitro and in vivo. Nucleotide alterations can be edited in the genomes of mammalian cells, and genetic switches can be designed to target the expression or excision of a [...] Read more.

Cre/loxP recombination is a well-established technique increasingly used for modifying DNA both in vitro and in vivo. Nucleotide alterations can be edited in the genomes of mammalian cells, and genetic switches can be designed to target the expression or excision of a gene in any tissue at any time in animal models. In this study, we propose a system which worked via the Cre/loxP switch gene and DsRed/emGFP dual-color fluorescence imaging. Mesenchymal stem cells (MSCs) can be used to regenerate damaged tissue because of their differentiation capacity. Although previous studies have presented evidence of fusion of transplanted MSCs with recipient cells, the possibility of fusion in such cases remains debated. Moreover, the effects and biological implications of the fusion of MSCs at the tissue and organ level have not yet been elucidated. Thus, the method for determining this issue is significant and the models we proposed can illustrate the question. However, the transgenic rats exhibited growth slower than that of wild-type rats over several weeks. The effects on the stemness, proliferation, cell cycle, and differentiation ability of bone marrow–derived rat MSCs (BM-rMSCs) from the models were examined to ensure our design was appropriate for the in vivo application. We demonstrated that MSC surface markers were maintained in DsRed and Cre transgenic rMSCs (DsRed-rMSCs and Cre-rMSCs, respectively). A WST-8 assay revealed decreased proliferative activity in these DsRed-rMSCs and Cre-rMSCs; this result was validated through cell counting. Furthermore, cell cycle analysis indicated a decrease in the proportion of G1-phase cells and a concomitant increase in the proportion of S-phase cells. The levels of cell cycle–related proteins also decreased in the DsRed-rMSCs and Cre-rMSCs, implying decelerated phase transition. However, the BM-rMSCs collected from the transgenic rats did not exhibit altered adipogenesis, osteogenesis, or chondrogenesis. The specific markers of these types of differentiation were upregulated after induction. Therefore, BM-rMSCs from DsRed and Cre transgenic models can be used to investigate the behavior of MSCs and related mechanisms. Such application may further the development of stem cell therapy for tissue damage and other diseases. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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21 pages, 2828 KiB

Open AccessArticle

Influence of Tamoxifen on Different Biological Pathways in Tumorigenesis and Transformation in Adipose-Derived Stem Cells, Mammary Cells and Mammary Carcinoma Cell Lines—An In Vitro Study

by Frederik Schlottmann, Vesna Bucan, Sarah Strauß, Felix Koop, Peter M. Vogt and Tobias R. Mett

Cells 2022, 11(17), 2733; https://doi.org/10.3390/cells11172733 - 1 Sep 2022

Cited by 2 | Viewed by 2188

Abstract

Breast carcinoma is one of the most common malignant tumors in women. In cases of hormone-sensitive cells, tamoxifen as an anti-estrogenic substance is a first line medication in the adjuvant setting. The spectrum of autologous breast reconstructions ranges from fat infiltrations to complex [...] Read more.

Breast carcinoma is one of the most common malignant tumors in women. In cases of hormone-sensitive cells, tamoxifen as an anti-estrogenic substance is a first line medication in the adjuvant setting. The spectrum of autologous breast reconstructions ranges from fat infiltrations to complex microsurgical procedures. The influence of adipose-derived stem cells (ASC) on the tumor bed and a possibly increased recurrence rate as a result are critically discussed. In addition, there is currently no conclusive recommendation regarding tamoxifen-treated patients and autologous fat infiltrations. The aim of the present study was to investigate the effect of tamoxifen on the gene expression of a variety of genes involved in tumorigenesis, cell growth and transformation. Mammary epithelial cell line and mammary carcinoma cell lines were treated with tamoxifen in vitro as well as co-cultured with ASC. Gene expression was quantified by PCR arrays and showed increased expression in the mammary carcinoma cell lines with increasing time of treatment and concentration of tamoxifen. The data presented can be considered as an addition to the controversial discussion on the relationship between ASC and breast carcinoma cells. Further studies are needed to quantify the in vivo interaction of ASC and mammary carcinoma cells and to conclusively assess the impact of tamoxifen in reconstructive cases with fat grafting. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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13 pages, 4321 KiB

Open AccessFeature PaperArticle

The Effects of Shear Force-Based Processing of Lipoaspirates on White Adipose Tissue and the Differentiation Potential of Adipose Derived Stem Cells

by Andreas Eigenberger, Oliver Felthaus, Thomas Schratzenstaller, Silke Haerteis, Kirsten Utpatel and Lukas Prantl

Cells 2022, 11(16), 2543; https://doi.org/10.3390/cells11162543 - 16 Aug 2022

Cited by 6 | Viewed by 2292

Abstract

Autologous lipotransfer is a promising method for tissue regeneration, because white adipose tissue contains a heterogeneous cell population, including mesenchymal stem cells, endothelial cells, immune cells, and adipocytes. In order to improve the outcome, adipose tissue can be processed before application. In this [...] Read more.

Autologous lipotransfer is a promising method for tissue regeneration, because white adipose tissue contains a heterogeneous cell population, including mesenchymal stem cells, endothelial cells, immune cells, and adipocytes. In order to improve the outcome, adipose tissue can be processed before application. In this study, we investigated changes caused by mechanical processing. Lipoaspirates were processed using sedimentation, first-time centrifugation, shear-force homogenization, and second-time centrifugation. The average adipocyte size, stromal vascular cell count, and adipocyte depot size were examined histologically at every processing step. In addition, the adipose derived stem cells (ADSCs) were isolated and differentiated osteogenically and adipogenically. While homogenization causes a disruption of adipocyte depots, the shape of the remaining adipocytes is not changed. On average, these adipocytes are smaller than the depot adipocytes, they are surrounded by the ECM, and therefore mechanically more stable. The volume loss of adipocyte depots leads to a significant enrichment of stromal vascular cells such as ADSCs. However, the mechanical processing does not change the potential of the ADSCs to differentiate adipogenically or osteogenically. It thus appears that mechanically processed lipoaspirates are promising for the reparation of even mechanically stressed tissue as that found in nasolabial folds. The changes resulting from the processing correspond more to a filtration of mechanically less stable components than to a manipulation of the tissue. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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16 pages, 3811 KiB

Open AccessArticle

Schwann Cells Promote Myogenic Differentiation of Myoblasts and Adipogenic Mesenchymal Stromal Cells on Poly-ɛ-Caprolactone-Collagen I-Nanofibers

by Aijia Cai, Zeng-Ming Zheng, Marcus Himmler, Dirk W. Schubert, Thomas A. Fuchsluger, Volker Weisbach, Raymund E. Horch and Andreas Arkudas

Cells 2022, 11(9), 1436; https://doi.org/10.3390/cells11091436 - 24 Apr 2022

Cited by 7 | Viewed by 2596

Abstract

For the purpose of skeletal muscle tissue engineering, different cell types have been investigated regarding their myogenic differentiation potential, including co-cultured myoblasts and adipogenic mesenchymal stromal cells (Mb/ADSC). As neural cells enhance synaptic junction formation, the aim of this study was to co-culture [...] Read more.

For the purpose of skeletal muscle tissue engineering, different cell types have been investigated regarding their myogenic differentiation potential, including co-cultured myoblasts and adipogenic mesenchymal stromal cells (Mb/ADSC). As neural cells enhance synaptic junction formation, the aim of this study was to co-culture Schwann cells (SCs) with Mb/ADSC on biocompatible electrospun aligned poly-ε-polycaprolacton (PCL)-collagen I-nanofibers. It was hypothesized that SCs, as part of the peripheral nervous system, promote the myogenic differentiation of Mb/ADSC co-cultures. Mb/ADSC were compared to Mb/ADSC/SC regarding their capacity for myogenic differentiation via immunofluorescent staining and gene expression of myogenic markers. Mb/ADSC/SC showed more myotubes after 28 days of differentiation (p ≤ 0.05). After 28 days of differentiation on electrospun aligned PCL-collagen I-nanofibers, gene expression of myosin heavy chains (MYH2) and myogenin (MYOG) was upregulated in Mb/ADSC/SC compared to Mb/ADSC (p ≤ 0.01 and p ≤ 0.05, respectively). Immunofluorescent staining for MHC showed highly aligned multinucleated cells as possible myotube formation in Mb/ADSC/SC. In conclusion, SCs promote myogenic differentiation of Mb/ADSC. The co-culture of primary Mb/ADSC/SC on PCL-collagen I-nanofibers serves as a physiological model for skeletal muscle tissue engineering, applicable to future clinical applications. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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13 pages, 5181 KiB

Open AccessArticle

Impact of Endothelial Progenitor Cells in the Vascularization of Osteogenic Scaffolds

by Dominik Steiner, Lea Reinhardt, Laura Fischer, Vanessa Popp, Carolin Körner, Carol I. Geppert, Tobias Bäuerle, Raymund E. Horch and Andreas Arkudas

Cells 2022, 11(6), 926; https://doi.org/10.3390/cells11060926 - 8 Mar 2022

Cited by 7 | Viewed by 3039

Abstract

The microvascular endothelial network plays an important role in osteogenesis, bone regeneration and bone tissue engineering. Endothelial progenitor cells (EPCs) display a high angiogenic and vasculogenic potential. The endothelialization of scaffolds with endothelial progenitor cells supports vascularization and tissue formation. In addition, EPCs [...] Read more.

The microvascular endothelial network plays an important role in osteogenesis, bone regeneration and bone tissue engineering. Endothelial progenitor cells (EPCs) display a high angiogenic and vasculogenic potential. The endothelialization of scaffolds with endothelial progenitor cells supports vascularization and tissue formation. In addition, EPCs enhance the osteogenic differentiation and bone formation of mesenchymal stem cells (MSCs). This study aimed to investigate the impact of EPCs on vascularization and bone formation of a hydroxyapatite (HA) and beta-tricalcium phosphate (ß-TCP)–fibrin scaffold. Three groups were designed: a scaffold-only group (A), a scaffold and EPC group (B), and a scaffold and EPC/MSC group (C). The HA/ß–TCP–fibrin scaffolds were placed in a porous titanium chamber permitting extrinsic vascularization from the surrounding tissue. Additionally, intrinsic vascularization was achieved by means of an arteriovenous loop (AV loop). After 12 weeks, the specimens were explanted and investigated by histology and CT. We were able to prove a strong scaffold vascularization in all groups. No differences regarding the vessel number and density were detected between the groups. Moreover, we were able to prove bone formation in the coimplantation group. Taken together, the AV loop is a powerful tool for vascularization which is independent from scaffold cellularization with endothelial progenitor cells’ prior implantation. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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Review

Jump to: Research, Other

12 pages, 565 KiB

Open AccessReview

Human Stem Cell Use in Androgenetic Alopecia: A Systematic Review

by Katarzyna Krefft-Trzciniecka, Zuzanna Piętowska, Danuta Nowicka and Jacek C. Szepietowski

Cells 2023, 12(6), 951; https://doi.org/10.3390/cells12060951 - 21 Mar 2023

Cited by 10 | Viewed by 6209

Abstract

Androgenetic alopecia is a condition that results in hair loss in both men and women. This can have a significant impact on a person’s psychological well-being, which can lead to a decreased quality of life. We conducted a systematic review to evaluate the [...] Read more.

Androgenetic alopecia is a condition that results in hair loss in both men and women. This can have a significant impact on a person’s psychological well-being, which can lead to a decreased quality of life. We conducted a systematic review to evaluate the efficacy of using stem cells in androgenic alopecia. The search was conducted in MEDLINE via PubMed, Web of Science, and Scopus databases. The review was performed on data pertaining to the efficacy of using different types of stem cells in androgenic alopecia: quantitative results of stem cell usage were compared to the control treatment or, different types of treatment for female and male androgenetic alopecia. Of the outcomes, the density of hair was analyzed. Fourteen articles were selected for this review. During and after treatment with stem cells, no major side effects were reported by patients with alopecia. The use of stem cells in androgenic alopecia seems to be a promising alternative to the standard treatment or it could play the role of complementary therapy to improve the effect of primary treatment. However, these results should be interpreted with caution until they can be reproduced in larger and more representative samples. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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23 pages, 1132 KiB

Open AccessReview

Chorioallantoic Membrane Assay at the Cross-Roads of Adipose-Tissue-Derived Stem Cell Research

by Dmytro Oliinyk, Andreas Eigenberger, Oliver Felthaus, Silke Haerteis and Lukas Prantl

Cells 2023, 12(4), 592; https://doi.org/10.3390/cells12040592 - 12 Feb 2023

Cited by 6 | Viewed by 4017

Abstract

With a history of more than 100 years of different applications in various scientific fields, the chicken chorioallantoic membrane (CAM) assay has proven itself to be an exceptional scientific model that meets the requirements of the replacement, reduction, and refinement principle (3R principle). [...] Read more.

With a history of more than 100 years of different applications in various scientific fields, the chicken chorioallantoic membrane (CAM) assay has proven itself to be an exceptional scientific model that meets the requirements of the replacement, reduction, and refinement principle (3R principle). As one of three extraembryonic avian membranes, the CAM is responsible for fetal respiration, metabolism, and protection. The model provides a unique constellation of immunological, vascular, and extracellular properties while being affordable and reliable at the same time. It can be utilized for research purposes in cancer biology, angiogenesis, virology, and toxicology and has recently been used for biochemistry, pharmaceutical research, and stem cell biology. Stem cells and, in particular, mesenchymal stem cells derived from adipose tissue (ADSCs) are emerging subjects for novel therapeutic strategies in the fields of tissue regeneration and personalized medicine. Because of their easy accessibility, differentiation profile, immunomodulatory properties, and cytokine repertoire, ADSCs have already been established for different preclinical applications in the files mentioned above. In this review, we aim to highlight and identify some of the cross-sections for the potential utilization of the CAM model for ADSC studies with a focus on wound healing and tissue engineering, as well as oncological research, e.g., sarcomas. Hereby, the focus lies on the combination of existing evidence and experience of such intersections with a potential utilization of the CAM model for further research on ADSCs. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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11 pages, 606 KiB

Open AccessReview

Cell-Enriched Lipotransfer (CELT) Improves Tissue Regeneration and Rejuvenation without Substantial Manipulation of the Adipose Tissue Graft

by Lukas Prantl, Andreas Eigenberger, Ruben Reinhard, Andreas Siegmund, Kerstin Heumann and Oliver Felthaus

Cells 2022, 11(19), 3159; https://doi.org/10.3390/cells11193159 - 8 Oct 2022

Cited by 6 | Viewed by 2256

Abstract

The good availability and the large content of adult stem cells in adipose tissue has made it one of the most interesting tissues in regenerative medicine. Although lipofilling is one of the most frequent procedures in plastic surgery, the method still struggles with [...] Read more.

The good availability and the large content of adult stem cells in adipose tissue has made it one of the most interesting tissues in regenerative medicine. Although lipofilling is one of the most frequent procedures in plastic surgery, the method still struggles with high absorption rates and volume losses of up to 70%. Therefore, many efforts have been made to optimize liposuction and to process the harvested tissue in order to increase fat graft retention. Because of their immunomodulatory properties, their cytokine secretory activity, and their differentiation potential, enrichment with adipose tissue-derived stem cells was identified as a promising tool to promote transplant survival. Here, we review the important parameters for lipofilling optimization. Finally, we present a new method for the enrichment of lipoaspirate with adipose tissue-derived stem cells and discuss the parameters that contribute to fat graft survival. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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23 pages, 5308 KiB

Open AccessReview

Autologous Stem Cells Transplants in the Treatment of Temporomandibular Joints Disorders: A Systematic Review and Meta-Analysis of Clinical Trials

by Maciej Chęciński, Kamila Chęcińska, Natalia Turosz, Monika Kamińska, Zuzanna Nowak, Maciej Sikora and Dariusz Chlubek

Cells 2022, 11(17), 2709; https://doi.org/10.3390/cells11172709 - 30 Aug 2022

Cited by 21 | Viewed by 4354

Abstract

This systematic review aims to analyze the outcomes of the treatment of temporomandibular joint (TMJ) articular pain (AP) and restricted maximum mouth opening (MMO) with intra-articular administration of mesenchymal stem cells (MSCs). The inclusion criteria allowed primary studies involving AP and/or MMO pre-treatment [...] Read more.

This systematic review aims to analyze the outcomes of the treatment of temporomandibular joint (TMJ) articular pain (AP) and restricted maximum mouth opening (MMO) with intra-articular administration of mesenchymal stem cells (MSCs). The inclusion criteria allowed primary studies involving AP and/or MMO pre-treatment and post-intervention values. Medical databases that were covered by ACM Digital, BASE, EBSCOhost, Google Scholar, PubMed, Scopus, and Web of Science engines were searched. The risk of bias was assessed with RoB 2 and ROBINS-I tools. The results were tabulated, plotted, and analyzed for regression. A total of 5 studies involving 51 patients/69 TMJs were identified, and 4 studies on 50 patients/67 TMJs were synthesized. Interventions were each time effective in decreasing AP and increasing MMO in a 6-month follow-up period by an average of about 85% and over 40%, respectively. Regression analysis showed a good fit of the logarithmic model for AP relief (5.8 − 0.8 ln x; R² = 0.90) and MMO increase (33.5 + 2.4 ln x; R² = 0.89). The results for AP and MMO were based on 3 studies in 39 patients and 4 studies in 50 patients, respectively, all at high risk of bias. The intra-articular administration of MSCs to TMJs, based on weak evidence, may be highly effective in reducing AP and improving MMO. This study received no funding. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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Other

Jump to: Research, Review

20 pages, 1721 KiB

Open AccessSystematic Review

Mesenchymal Stromal Cells Laden in Hydrogels for Osteoarthritis Cartilage Regeneration: A Systematic Review from In Vitro Studies to Clinical Applications

by Cristina Manferdini, Elena Gabusi, Yasmin Saleh, Enrico Lenzi, Giovanni D’Atri, Leonardo Ricotti and Gina Lisignoli

Cells 2022, 11(24), 3969; https://doi.org/10.3390/cells11243969 - 8 Dec 2022

Cited by 10 | Viewed by 2483

Abstract

This systematic review is focused on the main characteristics of the hydrogels used for embedding the mesenchymal stromal cells (MSCs) in in vitro/ex vivo studies, in vivo OA models and clinical trials for favoring cartilage regeneration in osteoarthritis (OA). PubMED and Embase databases [...] Read more.

This systematic review is focused on the main characteristics of the hydrogels used for embedding the mesenchymal stromal cells (MSCs) in in vitro/ex vivo studies, in vivo OA models and clinical trials for favoring cartilage regeneration in osteoarthritis (OA). PubMED and Embase databases were used to select the papers that were submitted to a public reference manager Rayyan Systematic Review Screening Software. A total of 42 studies were considered eligible: 25 articles concerned in vitro studies, 2 in vitro and ex vivo ones, 5 in vitro and in vivo ones, 8 in vivo ones and 2 clinical trials. Some in vitro studies evidenced a rheological characterization of the hydrogels and description of the crosslinking methods. Only 37.5% of the studies considered at the same time chondrogenic, fibrotic and hypertrophic markers. Ex vivo studies focused on hydrogel adhesion properties and the modification of MSC-laden hydrogels subjected to compression tests. In vivo studies evidenced the effect of cell-laden hydrogels in OA animal models or defined the chondrogenic potentiality of the cells in subcutaneous implantation models. Clinical studies confirmed the positive impact of these treatments on patients with OA. To speed the translation to the clinical use of cell-laden hydrogels, further studies on hydrogel characteristics, injection modalities, chemo-attractant properties and adhesion strength are needed. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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Open AccessSystematic Review

Methodological Flaws in Meta-Analyses of Clinical Studies on the Management of Knee Osteoarthritis with Stem Cells: A Systematic Review

by Christoph Schmitz, Christopher Alt, David A. Pearce, John P. Furia, Nicola Maffulli and Eckhard U. Alt

Cells 2022, 11(6), 965; https://doi.org/10.3390/cells11060965 - 11 Mar 2022

Cited by 15 | Viewed by 5592

Abstract

(1) Background: Conclusions of meta-analyses of clinical studies may substantially influence opinions of prospective patients and stakeholders in healthcare. Nineteen meta-analyses of clinical studies on the management of primary knee osteoarthritis (pkOA) with stem cells, published between January 2020 and July 2021, came [...] Read more.

(1) Background: Conclusions of meta-analyses of clinical studies may substantially influence opinions of prospective patients and stakeholders in healthcare. Nineteen meta-analyses of clinical studies on the management of primary knee osteoarthritis (pkOA) with stem cells, published between January 2020 and July 2021, came to inconsistent conclusions regarding the efficacy of this treatment modality. It is possible that a separate meta-analysis based on an independent, systematic assessment of clinical studies on the management of pkOA with stem cells may reach a different conclusion. (2) Methods: PubMed, Web of Science, and the Cochrane Library were systematically searched for clinical studies and meta-analyses of clinical studies on the management of pkOA with stem cells. All clinical studies and meta-analyses identified were evaluated in detail, as were all sub-analyses included in the meta-analyses. (3) Results: The inconsistent conclusions regarding the efficacy of treating pkOA with stem cells in the 19 assessed meta-analyses were most probably based on substantial differences in literature search strategies among different authors, misconceptions about meta-analyses themselves, and misconceptions about the comparability of different types of stem cells with regard to their safety and regenerative potential. An independent, systematic review of the literature yielded a total of 183 studies, of which 33 were randomized clinical trials, including a total of 6860 patients with pkOA. However, it was not possible to perform a scientifically sound meta-analysis. (4) Conclusions: Clinicians should interpret the results of the 19 assessed meta-analyses of clinical studies on the management of pkOA with stem cells with caution and should be cautious of the conclusions drawn therein. Clinicians and researchers should strive to participate in FDA and/or EMA reviewed and approved clinical trials to provide clinically and statistically valid efficacy. Full article

(This article belongs to the Special Issue Regeneration of Tissue with Mesenchymal Stem Cells)

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