Editorial

3 pages, 173 KiB

Open AccessEditorial

Introduction to the Special Issue on Stem Cell and Biologic Scaffold Engineering

by Panagiotis Mallis, Catherine Stavropoulos-Giokas and Efstathios Michalopoulos

Bioengineering 2019, 6(3), 72; https://doi.org/10.3390/bioengineering6030072 - 21 Aug 2019

Cited by 2 | Viewed by 4777

Tissue engineering and regenerative medicine is a rapidly evolving research field that effectively combines stem cells and biologic scaffolds in order to replace damaged tissues. Biologic scaffolds can be produced through the removal of resident cellular populations using several tissue engineering approaches, such [...] Read more.

Tissue engineering and regenerative medicine is a rapidly evolving research field that effectively combines stem cells and biologic scaffolds in order to replace damaged tissues. Biologic scaffolds can be produced through the removal of resident cellular populations using several tissue engineering approaches, such as the decellularization method. In addition, tissue engineering requires the interaction of biologic scaffolds with cellular populations. Stem cells are characterized by unlimited cell division, self-renewal, and differentiation potential, distinguishing themselves as a frontline source for the repopulation of decellularized matrices and scaffolds. However, parameters such as stem cell number, in vitro cultivation conditions, and specific growth media composition need further evaluation. The ultimate goal is the development of “artificial” tissues similar to native ones, which is achieved by properly combining stem cells and biologic scaffolds, thus bringing artificial tissues one step closer to personalized medicine. In this special issue of Bioengineering, we highlight the beneficial effects of stem cells and scaffolds in the emerging field of tissue engineering. The current issue includes articles regarding the use of stem cells in tissue engineering approaches and the proper production of biologically based scaffolds like nerve conduit, esophageal scaffold, and fibrin gel. Full article

(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)

Research

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19 pages, 3300 KiB

Open AccessArticle

Multifactorial Modeling Reveals a Dominant Role of Wnt Signaling in Lineage Commitment of Human Pluripotent Stem Cells

by Tiago P. Dias, Tiago G. Fernandes, Maria Margarida Diogo and Joaquim M. S. Cabral

Bioengineering 2019, 6(3), 71; https://doi.org/10.3390/bioengineering6030071 - 15 Aug 2019

Cited by 5 | Viewed by 7096

Abstract

The human primed pluripotent state is maintained by a complex balance of several signaling pathways governing pluripotency maintenance and commitment. Here, we explore a multiparameter approach using a full factorial design and a simple well-defined culture system to assess individual and synergistic contributions [...] Read more.

The human primed pluripotent state is maintained by a complex balance of several signaling pathways governing pluripotency maintenance and commitment. Here, we explore a multiparameter approach using a full factorial design and a simple well-defined culture system to assess individual and synergistic contributions of Wnt, FGF and TGFβ signaling to pluripotency and lineage specification of human induced pluripotent stem cells (hiPSC). Hierarchical clustering and quadratic models highlighted a dominant effect of Wnt signaling over FGF and TGFβ signaling, drawing hiPSCs towards mesendoderm lineages. In addition, a synergistic effect between Wnt signaling and FGF was observed to have a negative contribution to pluripotency maintenance and a positive contribution to ectoderm and mesoderm commitment. Furthermore, FGF and TGFβ signaling only contributed significantly for negative ectoderm scores, suggesting that the effect of both factors for pluripotency maintenance resides in a balance of inhibitory signals instead of proactive stimulation of hiPSC pluripotency. Overall, our dry-signaling multiparameter modeling approach can contribute to elucidate individual and synergistic inputs, providing an additional degree of comprehension of the complex regulatory mechanisms of human pluripotency and commitment. Full article

(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)

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13 pages, 2140 KiB

Open AccessArticle

Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study

by Vassilis Protogerou, Efstathios Michalopoulos, Panagiotis Mallis, Ioanna Gontika, Zetta Dimou, Christos Liakouras, Catherine Stavropoulos-Giokas, Nikolaos Kostakopoulos, Michael Chrisofos and Charalampos Deliveliotis

Bioengineering 2019, 6(1), 21; https://doi.org/10.3390/bioengineering6010021 - 05 Mar 2019

Cited by 30 | Viewed by 7447

Abstract

Erectile dysfunction (ED) affects more than 30 million men; endothelial dysfunction plays a significant role in EDs pathogenesis. The aim of this study was to administer mesenchymal stem cells (MSC) derived from adipose tissue and platelet lysate (PL) into patients with erectile dysfunction. [...] Read more.

Erectile dysfunction (ED) affects more than 30 million men; endothelial dysfunction plays a significant role in EDs pathogenesis. The aim of this study was to administer mesenchymal stem cells (MSC) derived from adipose tissue and platelet lysate (PL) into patients with erectile dysfunction. This pilot study enrolled eight patients with diagnosed ED. Patients enrolled were suffering from organic ED due to diabetes melitus, hypertension, hypercholesterolaemia, and Peyronie disease. The patients were distributed in 2 groups. Patients in group A received adipose derived mesenchymal stem cells (ADMSC) resuspended in PL while patients in group B received only PL. ADMSCs were isolated from patients’ adipose tissue and expanded. In addition, blood sampling was obtained from the patients in order to isolate platelet lysate. After the application of the above treatments, patients were evaluated with an International Index of Erectile Function (IIEF-5) questionnaire, penile triplex, and reported morning erections. After MSCs and PL administration, patients presented improved erectile function after 1 and 3 months of follow-up. A statistically significant difference was observed in the IIEF-5 score before and after administration of both treatments after the first month (p < 0.05) and the third month (p < 0.05). No statistically significant difference was observed in the IIEF-5 score between group A and B patients. All patients were characterized by improved penile triplex and increased morning erections. No severe adverse reactions were observed in any patient except a minor pain at the site of injection, which was in the limits of tolerability. The results of this study indicated the satisfactory use of MSCs and PL in ED. MSCs in combination with PL or PL alone seems to be very promising, especially without having the negative effects of the current therapeutic treatment. Full article

(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)

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10 pages, 1445 KiB

Open AccessCommunication

Optimization of Decellularization Procedure in Rat Esophagus for Possible Development of a Tissue Engineered Construct

by Panagiotis Mallis, Panagiota Chachlaki, Michalis Katsimpoulas, Catherine Stavropoulos-Giokas and Efstathios Michalopoulos

Bioengineering 2019, 6(1), 3; https://doi.org/10.3390/bioengineering6010003 - 24 Dec 2018

Cited by 16 | Viewed by 4774

Abstract

Background: Current esophageal treatment is associated with significant morbidity. The gold standard therapeutic strategies are stomach interposition or autografts derived from the jejunum and colon. However, severe adverse reactions, such as esophageal leakage, stenosis and infection, accompany the above treatments, which, most times, [...] Read more.

Background: Current esophageal treatment is associated with significant morbidity. The gold standard therapeutic strategies are stomach interposition or autografts derived from the jejunum and colon. However, severe adverse reactions, such as esophageal leakage, stenosis and infection, accompany the above treatments, which, most times, are life threating. The aim of this study was the optimization of a decellularization protocol in order to develop a proper esophageal tissue engineered construct. Methods: Rat esophagi were obtained from animals and were decellularized. The decellularization process involved the use of 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) and sodium dodecyl sulfate (SDS) buffers for 6 h each, followed by incubation in a serum medium. The whole process involved two decellularization cycles. Then, a histological analysis was performed. In addition, the amounts of collagen, sulphated glycosaminoglycans and DNA content were quantified. Results: The histological analysis revealed that only the first decellularization cycle was enough to produce a cellular and nuclei free esophageal scaffold with a proper extracellular matrix orientation. These results were further confirmed by biochemical quantification. Conclusions: Based on the above results, the current decellularization protocol can be applied successfully in order to produce an esophageal tissue engineered construct. Full article

(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)

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12 pages, 3150 KiB

Open AccessArticle

Decellularized Human Umbilical Artery Used as Nerve Conduit

by Ioanna Gontika, Michalis Katsimpoulas, Efstathios Antoniou, Alkiviadis Kostakis, Catherine Stavropoulos-Giokas and Efstathios Michalopoulos

Bioengineering 2018, 5(4), 100; https://doi.org/10.3390/bioengineering5040100 - 21 Nov 2018

Cited by 8 | Viewed by 5144

Abstract

Treatment of injuries to peripheral nerves after a segmental defect is one of the most challenging surgical problems. Despite advancements in microsurgical techniques, complete recovery of nerve function after repair has not been achieved. The purpose of this study was to evaluate the [...] Read more.

Treatment of injuries to peripheral nerves after a segmental defect is one of the most challenging surgical problems. Despite advancements in microsurgical techniques, complete recovery of nerve function after repair has not been achieved. The purpose of this study was to evaluate the use of the decellularized human umbilical artery (hUA) as nerve guidance conduit. A segmental peripheral nerve injury was created in 24 Sprague–Dawley rats. The animals were organized into two experimental groups with different forms of repair: decellularized hUA (n = 12), and autologous nerve graft (n = 12). Sciatic faction index and gastrocnemius muscle values were calculated for functional recovery evaluation. Nerve morphometry was used to analyze nerve regeneration. Results showed that decellularized hUAs after implantation were rich in nerve fibers and characterized by improved Sciatic Functional index (SFI) values. Decellularized hUA may support elongation and bridging of the 10 mm nerve gap. Full article

(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)

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16 pages, 7771 KiB

Open AccessArticle

Evaluation of HLA-G Expression in Multipotent Mesenchymal Stromal Cells Derived from Vitrified Wharton’s Jelly Tissue

by Panagiotis Mallis, Dimitra Boulari, Efstathios Michalopoulos, Amalia Dinou, Maria Spyropoulou-Vlachou and Catherine Stavropoulos-Giokas

Bioengineering 2018, 5(4), 95; https://doi.org/10.3390/bioengineering5040095 - 01 Nov 2018

Cited by 12 | Viewed by 5512

Abstract

Background: Mesenchymal Stromal Cells (MSCs) from Wharton’s Jelly (WJ) tissue express HLA-G, a molecule which exerts several immunological properties. This study aimed at the evaluation of HLA-G expression in MSCs derived from vitrified WJ tissue. Methods: WJ tissue samples were isolated from human [...] Read more.

Background: Mesenchymal Stromal Cells (MSCs) from Wharton’s Jelly (WJ) tissue express HLA-G, a molecule which exerts several immunological properties. This study aimed at the evaluation of HLA-G expression in MSCs derived from vitrified WJ tissue. Methods: WJ tissue samples were isolated from human umbilical cords, vitrified with the use of VS55 solution and stored for 1 year at −196 °C. After 1 year of storage, the WJ tissue was thawed and MSCs were isolated. Then, MSCs were expanded until reaching passage 8, followed by estimation of cell number, cell doubling time (CDT), population doubling (PD) and cell viability. In addition, multilineage differentiation, Colony-Forming Units (CFUs) assay and immunophenotypic analyses were performed. HLA-G expression in MSCs derived from vitrified samples was evaluated by immunohistochemistry, RT-PCR/PCR, mixed lymphocyte reaction (MLR) and immunofluorescence. MSCs derived from non-vitrified WJ tissue were used in order to validate the results obtained from the above methods. Results: MSCs were successfully obtained from vitrified WJ tissues retaining their morphological and multilineage differentiation properties. Furthermore, MSCs from vitrified WJ tissues successfully expressed HLA-G. Conclusion: The above results indicated the successful expression of HLA-G by MSCs from vitrified WJ tissues, thus making them ideal candidates for immunomodulation. Full article

(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)

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Other

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14 pages, 1476 KiB

Open AccessTechnical Note

Short Term Results of Fibrin Gel Obtained from Cord Blood Units: A Preliminary in Vitro Study

by Panagiotis Mallis, Ioanna Gontika, Zetta Dimou, Effrosyni Panagouli, Jerome Zoidakis, Manousos Makridakis, Antonia Vlahou, Eleni Georgiou, Vasiliki Gkioka, Catherine Stavropoulos-Giokas and Efstathios Michalopoulos

Bioengineering 2019, 6(3), 66; https://doi.org/10.3390/bioengineering6030066 - 02 Aug 2019

Cited by 13 | Viewed by 6570

Abstract

Background: Recent findings have shown that the fibrin gel derived from cord blood units (CBUs) play a significant role in wound healing and tissue regeneration. The aim of this study was to standardize the fibrin gel production process in order to allow for [...] Read more.

Background: Recent findings have shown that the fibrin gel derived from cord blood units (CBUs) play a significant role in wound healing and tissue regeneration. The aim of this study was to standardize the fibrin gel production process in order to allow for its regular use. Methods: CBUs (n = 200) were assigned to 4 groups according to their initial volume. Then, a two-stage centrifugation protocol was applied in order to obtain platelet rich plasma (PRP). The concentration of platelets (PLTs), white blood cells (WBCs) and red blood cells (RBCs) were determined prior to and after the production process. In addition, targeted proteomic analysis using multiple reaction monitoring was performed. Finally, an appropriate volume of calcium gluconate was used in PRP for the production of fibrin gel. Results: The results of this study showed that high volume CBUs were characterized by greater recovery rates, concentration and number of PLTs compared to the low volume CBUs. Proteomic analysis revealed the presence of key proteins for regenerative medicine. Fibrin gel was successfully produced from CBUs of all groups. Conclusion: In this study, low volume CBUs could be an alternative source for the production of fibrin gel, which can be used in multiple regenerative medicine approaches. Full article

(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)

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10 pages, 202 KiB

Open AccessOpinion

Introducing the Language of “Relativity” for New Scaffold Categorization

by Haobo Yuan

Bioengineering 2019, 6(1), 20; https://doi.org/10.3390/bioengineering6010020 - 26 Feb 2019

Cited by 4 | Viewed by 4344

Abstract

Research related with scaffold engineering tends to be cross-domain and miscellaneous. Several realms may need to be focused simultaneously, including biomedicine for cell culture and 3D scaffold, physics for dynamics, manufacturing for technologies like 3D printing, chemistry for material composition, as well as [...] Read more.

Research related with scaffold engineering tends to be cross-domain and miscellaneous. Several realms may need to be focused simultaneously, including biomedicine for cell culture and 3D scaffold, physics for dynamics, manufacturing for technologies like 3D printing, chemistry for material composition, as well as architecture for scaffold’s geometric control. As a result, researchers with different backgrounds sometimes could have different understanding towards the product described as ‘Scaffold’. After reviewing the literature, numerous studies termed their developed scaffold as ‘novel’, compared with scaffolds previously designed by others using comparing criterion like ‘research time’, ‘manufacturing method’, ‘geometry’, and so on. While it may have been convenient a decade ago to, for example, categorize scaffold with ‘Dualistic Thinking’ logic into ‘simple-complicated’ or ‘traditional-novel’, this method for categorizing ‘novelty’ and distinguishing scaffold is insufficiently persuasive and precise when it comes to modern or future scaffold. From this departure of philosophical language, namely the language of ‘relativity’, it is important to distinguish between different scaffolds. Other than attempting to avoid ambiguity in perceiving scaffold, this language also provides clarity regarding the ‘evolution stage’ where the focused scaffolds currently stand, where they have been developed, and where in future they could possibly evolve. Full article

(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)

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