Pharmaceutics

Research

Jump to: Review

16 pages, 3953 KiB

Open AccessArticle

Effervescent Atomizer as Novel Cell Spray Technology to Decrease the Gas-to-Liquid Ratio

by Anja Lena Thiebes, Sarah Klein, Jonas Zingsheim, Georg H. Möller, Stefanie Gürzing, Manuel A. Reddemann, Mehdi Behbahani, Stefan Jockenhoevel and Christian G. Cornelissen

Pharmaceutics 2022, 14(11), 2421; https://doi.org/10.3390/pharmaceutics14112421 - 09 Nov 2022

Cited by 3 | Viewed by 1581

Abstract

Cell spraying has become a feasible application method for cell therapy and tissue engineering approaches. Different devices have been used with varying success. Often, twin-fluid atomizers are used, which require a high gas velocity for optimal aerosolization characteristics. To decrease the amount and [...] Read more.

Cell spraying has become a feasible application method for cell therapy and tissue engineering approaches. Different devices have been used with varying success. Often, twin-fluid atomizers are used, which require a high gas velocity for optimal aerosolization characteristics. To decrease the amount and velocity of required air, a custom-made atomizer was designed based on the effervescent principle. Different designs were evaluated regarding spray characteristics and their influence on human adipose-derived mesenchymal stromal cells. The arithmetic mean diameters of the droplets were 15.4–33.5 µm with decreasing diameters for increasing gas-to-liquid ratios. The survival rate was >90% of the control for the lowest gas-to-liquid ratio. For higher ratios, cell survival decreased to approximately 50%. Further experiments were performed with the design, which had shown the highest survival rates. After seven days, no significant differences in metabolic activity were observed. The apoptosis rates were not influenced by aerosolization, while high gas-to-liquid ratios caused increased necrosis levels. Tri-lineage differentiation potential into adipocytes, chondrocytes, and osteoblasts was not negatively influenced by aerosolization. Thus, the effervescent aerosolization principle was proven suitable for cell applications requiring reduced amounts of supplied air. This is the first time an effervescent atomizer was used for cell processing. Full article

(This article belongs to the Special Issue Stromal, Stem, Signaling Cells: The Multiple Roles and Applications of Mesenchymal Cells)

► Show Figures

Figure 1

16 pages, 9561 KiB

Open AccessArticle

Autologous Marrow Mesenchymal Stem Cell Driving Bone Regeneration in a Rabbit Model of Femoral Head Osteonecrosis

by Ilenia Mastrolia, Andrea Giorgini, Alba Murgia, Pietro Loschi, Tiziana Petrachi, Valeria Rasini, Massimo Pinelli, Valentina Pinto, Francesca Lolli, Chiara Chiavelli, Giulia Grisendi, Maria Cristina Baschieri, Giorgio De Santis, Fabio Catani, Massimo Dominici and Elena Veronesi

Pharmaceutics 2022, 14(10), 2127; https://doi.org/10.3390/pharmaceutics14102127 - 06 Oct 2022

Cited by 2 | Viewed by 1845

Abstract

Osteonecrosis of the femoral head (ONFH) is a progressive degenerative disease that ultimately requires a total hip replacement. Mesenchymal stromal/stem cells (MSCs), particularly the ones isolated from bone marrow (BM), could be promising tools to restore bone tissue in ONFH. Here, we established [...] Read more.

Osteonecrosis of the femoral head (ONFH) is a progressive degenerative disease that ultimately requires a total hip replacement. Mesenchymal stromal/stem cells (MSCs), particularly the ones isolated from bone marrow (BM), could be promising tools to restore bone tissue in ONFH. Here, we established a rabbit model to mimic the pathogenic features of human ONFH and to challenge an autologous MSC-based treatment. ON has been originally induced by the synergic combination of surgery and steroid administration. Autologous BM-MSCs were then implanted in the FH, aiming to restore the damaged tissue. Histological analyses confirmed bone formation in the BM-MSC treated rabbit femurs but not in the controls. In addition, the model also allowed investigations on BM-MSCs isolated before (ON-BM-MSCs) and after (ON+BM-MSCs) ON induction to dissect the impact of ON damage on MSC behavior in an affected microenvironment, accounting for those clinical approaches foreseeing MSCs generally isolated from affected patients. BM-MSCs, isolated before and after ON induction, revealed similar growth rates, immunophenotypic profiles, and differentiation abilities regardless of the ON. Our data support the use of ON+BM-MSCs as a promising autologous therapeutic tool to treat ON, paving the way for a more consolidated use into the clinical settings. Full article

(This article belongs to the Special Issue Stromal, Stem, Signaling Cells: The Multiple Roles and Applications of Mesenchymal Cells)

► Show Figures

Graphical abstract

18 pages, 2396 KiB

Open AccessArticle

PSME4 Degrades Acetylated YAP1 in the Nucleus of Mesenchymal Stem Cells

by Yong Sook Kim, Mira Kim, Dong Im Cho, Soo Yeon Lim, Ju Hee Jun, Mi Ra Kim, Bo Gyeong Kang, Gwang Hyeon Eom, Gaeun Kang, Somy Yoon and Youngkeun Ahn

Pharmaceutics 2022, 14(8), 1659; https://doi.org/10.3390/pharmaceutics14081659 - 09 Aug 2022

Cited by 2 | Viewed by 1864

Abstract

Intensive research has focused on minimizing the infarct area and stimulating endogenous regeneration after myocardial infarction. Our group previously elucidated that apicidin, a histone deacetylase (HDAC) inhibitor, robustly accelerates the cardiac commitment of naïve mesenchymal stem cells (MSCs) through acute loss of YAP1. [...] Read more.

Intensive research has focused on minimizing the infarct area and stimulating endogenous regeneration after myocardial infarction. Our group previously elucidated that apicidin, a histone deacetylase (HDAC) inhibitor, robustly accelerates the cardiac commitment of naïve mesenchymal stem cells (MSCs) through acute loss of YAP1. Here, we propose the novel regulation of YAP1 in MSCs. We found that acute loss of YAP1 after apicidin treatment resulted in the mixed effects of transcriptional arrest and proteasomal degradation. Subcellular fractionation revealed that YAP1 was primarily localized in the cytoplasm. YAP1 was acutely relocalized into the nucleus and underwent proteasomal degradation. Interestingly, phosphor-S127 YAP1 was shuttled into the nucleus, suggesting that a mechanism other than phosphorylation governed the subcellular localization of YAP1. Apicidin successfully induced acetylation and subsequent dissociation of YAP1 from 14-3-3, an essential molecule for cytoplasmic restriction. HDAC6 regulated both acetylation and subcellular localization of YAP1. An acetylation-dead mutant of YAP1 retarded nuclear redistribution upon apicidin treatment. We failed to acquire convincing evidence for polyubiquitination-dependent degradation of YAP1, suggesting that a polyubiquitination-independent regulator determined YAP1 fate. Nuclear PSME4, a subunit of the 26 S proteasome, recognized and degraded acetyl YAP1 in the nucleus. MSCs from PSME4-null mice were injected into infarcted heart, and aberrant sudden death was observed. Injection of immortalized human MSCs after knocking down PSME4 failed to improve either cardiac function or the fibrotic scar area. Our data suggest that acetylation-dependent proteasome subunit PSME4 clears acetyl-YAP1 in response to apicidin treatment in the nucleus of MSCs. Full article

(This article belongs to the Special Issue Stromal, Stem, Signaling Cells: The Multiple Roles and Applications of Mesenchymal Cells)

► Show Figures

Figure 1

12 pages, 2244 KiB

Open AccessArticle

Exosomes Derived from Dental Pulp Stem Cells Show Different Angiogenic and Osteogenic Properties in Relation to the Age of the Donor

by Giulia Brunello, Federica Zanotti, Martina Trentini, Ilaria Zanolla, Elham Pishavar, Vittorio Favero, Riccardo Favero, Lorenzo Favero, Eriberto Bressan, Massimo Bonora, Stefano Sivolella and Barbara Zavan

Pharmaceutics 2022, 14(5), 908; https://doi.org/10.3390/pharmaceutics14050908 - 21 Apr 2022

Cited by 15 | Viewed by 2653

Abstract

Craniofacial tissue reconstruction still represents a challenge in regenerative medicine. Mesenchymal stem cell (MSC)-based tissue engineering strategies have been introduced to enhance bone tissue repair. However, the risk of related complications is limiting their usage. To overcome these drawbacks, exosomes (EXOs) derived from [...] Read more.

Craniofacial tissue reconstruction still represents a challenge in regenerative medicine. Mesenchymal stem cell (MSC)-based tissue engineering strategies have been introduced to enhance bone tissue repair. However, the risk of related complications is limiting their usage. To overcome these drawbacks, exosomes (EXOs) derived from MSCs have been recently proposed as a cell-free alternative to MSCs to direct tissue regeneration. It was hypothesized that there is a correlation between the biological properties of exosomes derived from the dental pulp and the age of the donor. The aim of the study was to investigate the effect of EXOs derived from dental pulp stem cells of permanent teeth (old donor group) or exfoliated deciduous teeth (young donor group) on MSCs cultured in vitro. Proliferation potential was evaluated by doubling time, and commitment ability by gene expression and biochemical quantification for tissue-specific factors. Results showed a well-defined proliferative influence for the younger donor aged group. Similarly, a higher commitment ability was detected in the young group. In conclusion, EXOs could be employed to promote bone regeneration, likely playing an important role in neo-angiogenesis in early healing phases. Full article

(This article belongs to the Special Issue Stromal, Stem, Signaling Cells: The Multiple Roles and Applications of Mesenchymal Cells)

► Show Figures

Figure 1

17 pages, 1801 KiB

Open AccessArticle

Influence of Periodontal Ligament Stem Cell-Derived Conditioned Medium on Osteoblasts

by Solen Novello, Sylvie Tricot-Doleux, Agnès Novella, Pascal Pellen-Mussi and Sylvie Jeanne

Pharmaceutics 2022, 14(4), 729; https://doi.org/10.3390/pharmaceutics14040729 - 28 Mar 2022

Cited by 10 | Viewed by 2122

Abstract

Mesenchymal stem cells (MSC) are involved in the regeneration of various missing or compromised periodontal tissues, including bone. MSC-derived conditioned medium (CM) has recently been explored as a favorable surrogate for stem cell therapy, as it is capable of producing comparable therapeutic effects. [...] Read more.

Mesenchymal stem cells (MSC) are involved in the regeneration of various missing or compromised periodontal tissues, including bone. MSC-derived conditioned medium (CM) has recently been explored as a favorable surrogate for stem cell therapy, as it is capable of producing comparable therapeutic effects. This study aimed to evaluate the influence of periodontal ligament stem cells (PDLSC)-CM on osteoblasts (OB) and its potential as a therapeutic tool for periodontal regeneration. Human PDLSC were isolated and characterized, and CM from these cells was collected. The presence of exosomes in the culture supernatant was observed by immunofluorescence and by transmission electron microscopy. CM was added to a cultured osteoblastic cell line (Saos-2 cells) and viability (MTT assay) and gene expression analysis (real-time PCR) were examined. A cell line derived from the periodontal ligament and showing all the characteristics of MSC was successfully isolated and characterized. The addition of PDLSC-CM to Saos-2 cells led to an enhancement of their proliferation and an increased expression of some osteoblastic differentiation markers, but this differentiation was not complete. Saos-2 cells were involved in the initial inflammation process by releasing IL-6 and activating COX2. The effects of PDLSC-CM on Saos-2 appear to arise from a cumulative effect of different effective components rather than a few factors present at high levels. Full article

(This article belongs to the Special Issue Stromal, Stem, Signaling Cells: The Multiple Roles and Applications of Mesenchymal Cells)

► Show Figures

Figure 1

Review

Jump to: Research

13 pages, 625 KiB

Open AccessReview

Searching for the Optimal Donor for Allogenic Adipose-Derived Stem Cells: A Comprehensive Review

by Tihomir Georgiev-Hristov, Mariano García-Arranz, Jacobo Trébol-López, Paula Barba-Recreo and Damián García-Olmo

Pharmaceutics 2022, 14(11), 2338; https://doi.org/10.3390/pharmaceutics14112338 - 29 Oct 2022

Cited by 4 | Viewed by 1351

Abstract

Adipose-derived stem cells comprise several clinically beneficial qualities that have been explored in basic research and have motivated several clinical studies with promising results. After being approved in the European Union, UK, Switzerland, Israel, and Japan, allogeneic adipose-derived stem cells (darvadstrocel) have been [...] Read more.

Adipose-derived stem cells comprise several clinically beneficial qualities that have been explored in basic research and have motivated several clinical studies with promising results. After being approved in the European Union, UK, Switzerland, Israel, and Japan, allogeneic adipose-derived stem cells (darvadstrocel) have been recently granted a regenerative medicine advanced therapy (RMAT) designation by US FDA for complex perianal fistulas in adults with Crohn’s disease. This huge scientific step is likely to impact the future spread of the indications of allogeneic adipose-derived stem cell applications. The current knowledge on adipose stem cell harvest describes quantitative and qualitative differences that could be influenced by different donor conditions and donor sites. In this comprehensive review, we summarize the current knowledge on the topic and propose donor profiles that could provide the optimal initial quality of this living drug, as a starting point for further applications and studies in different pathological conditions. Full article

(This article belongs to the Special Issue Stromal, Stem, Signaling Cells: The Multiple Roles and Applications of Mesenchymal Cells)

► Show Figures

Figure 1

18 pages, 734 KiB

Open AccessReview

Mesenchymal Stem/Stromal Cells in Organ Transplantation

by Dayanand Deo, Misty Marchioni and Prakash Rao

Pharmaceutics 2022, 14(4), 791; https://doi.org/10.3390/pharmaceutics14040791 - 04 Apr 2022

Cited by 9 | Viewed by 2732

Abstract

Organ transplantation is essential and crucial for saving and enhancing the lives of individuals suffering from end-stage organ failure. Major challenges in the medical field include the shortage of organ donors, high rates of organ rejection, and long wait times. To address the [...] Read more.

Organ transplantation is essential and crucial for saving and enhancing the lives of individuals suffering from end-stage organ failure. Major challenges in the medical field include the shortage of organ donors, high rates of organ rejection, and long wait times. To address the current limitations and shortcomings, cellular therapy approaches have been developed using mesenchymal stem/stromal cells (MSC). MSC have been isolated from various sources, have the ability to differentiate to important cell lineages, have anti-inflammatory and immunomodulatory properties, allow immunosuppressive drug minimization, and induce immune tolerance towards the transplanted organ. Additionally, rapid advances in the fields of tissue engineering and regenerative medicine have emerged that focus on either generating new organs and organ sources or maximizing the availability of existing organs. This review gives an overview of the various properties of MSC that have enabled its use as a cellular therapy for organ preservation and transplant. We also highlight emerging fields of tissue engineering and regenerative medicine along with their multiple sub-disciplines, underlining recent advances, widespread clinical applications, and potential impact on the future of tissue and organ transplantation. Full article

(This article belongs to the Special Issue Stromal, Stem, Signaling Cells: The Multiple Roles and Applications of Mesenchymal Cells)

► Show Figures

Figure 1

25 pages, 1352 KiB

Open AccessReview

Advancing Regenerative Cellular Therapies in Non-Scarring Alopecia

by Talagavadi Channaiah Anudeep, Madhan Jeyaraman, Sathish Muthu, Ramya Lakshmi Rajendran, Prakash Gangadaran, Prabhu Chandra Mishra, Shilpa Sharma, Saurabh Kumar Jha and Byeong-Cheol Ahn

Pharmaceutics 2022, 14(3), 612; https://doi.org/10.3390/pharmaceutics14030612 - 10 Mar 2022

Cited by 15 | Viewed by 5864

Abstract

Alopecia or baldness is a common diagnosis in clinical practice. Alopecia can be scarring or non-scarring, diffuse or patchy. The most prevalent type of alopecia is non-scarring alopecia, with the majority of cases being androgenetic alopecia (AGA) or alopecia areata (AA). AGA is [...] Read more.

Alopecia or baldness is a common diagnosis in clinical practice. Alopecia can be scarring or non-scarring, diffuse or patchy. The most prevalent type of alopecia is non-scarring alopecia, with the majority of cases being androgenetic alopecia (AGA) or alopecia areata (AA). AGA is traditionally treated with minoxidil and finasteride, while AA is treated with immune modulators; however, both treatments have significant downsides. These drawbacks compel us to explore regenerative therapies that are relatively devoid of adverse effects. A thorough literature review was conducted to explore the existing proven and experimental regenerative treatment modalities in non-scarring alopecia. Multiple treatment options compelled us to classify them into growth factor-rich and stem cell-rich. The growth factor-rich group included platelet-rich plasma, stem cell-conditioned medium, exosomes and placental extract whereas adult stem cells (adipose-derived stem cell-nano fat and stromal vascular fraction; bone marrow stem cell and hair follicle stem cells) and perinatal stem cells (umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), Wharton jelly-derived MSCs (WJ-MSCs), amniotic fluid-derived MSCs (AF-MSCs), and placental MSCs) were grouped into the stem cell-rich group. Because of its regenerative and proliferative capabilities, MSC lies at the heart of regenerative cellular treatment for hair restoration. A literature review revealed that both adult and perinatal MSCs are successful as a mesotherapy for hair regrowth. However, there is a lack of standardization in terms of preparation, dose, and route of administration. To better understand the source and mode of action of regenerative cellular therapies in hair restoration, we have proposed the “À La Mode Classification”. In addition, available evidence-based cellular treatments for hair regrowth have been thoroughly described. Full article

(This article belongs to the Special Issue Stromal, Stem, Signaling Cells: The Multiple Roles and Applications of Mesenchymal Cells)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Stromal, Stem, Signaling Cells: The Multiple Roles and Applications of Mesenchymal Cells

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI