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Application of Nano- and Bio-materials in Cell-Based Therapy

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: closed (20 January 2022) | Viewed by 28994

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Special Issue Editors

Dr. Ana Isabel Flores

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Guest Editor

Instituto de Investigación Hospital 12 de Octubre i+12, Madrid, Spain
Interests: regenerative medicine; nanomedicine; mesenchymal stromal cells; targeted cell therapy; regeneration; cancer therapy

Dr. Juan Luis Paris

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Guest Editor

1. Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Málaga, Spain
2. Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain
Interests: nanomedicine; drug delivery; gene delivery; mesoporous silica; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Dr. Paz de la Torre

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Guest Editor

Instituto de Investigación Hospital 12 de Octubre i+12, Madrid, Spain
Interests: regenerative medicine; mesenchymal stromal cells; cell therapy; nanomedicine; perinatal tissues

Special Issue Information

Dear Colleagues,

Cell therapy strategies hold great promise for regenerative medicine and cancer immunotherapy, among other applications. In order to improve the potential of these cell therapies, their combination with materials science has brought a plethora of scientific advances in recent years. From the development of scaffolding materials for tissue regeneration in bone, cartilage, tendons tissue, and nerve tissue engineering, to the exploitation of cell migration properties to deliver drug-loaded nanoparticles for cancer therapy, the possibilities of this type of combinations appear to be almost endless.

In this Special Issue, we invite scientists to contribute original research articles or review articles that are related to the combination of nano- and biomaterials with cells for therapeutic purposes. Potential topics include, but are not limited to:

3D scaffolds seeded with cells for regenerative medicine
Nanoparticle delivery strategies based on living nanoparticle carriers (either mammalian cells or bacteria)
Nanoparticle-mediated non-viral genetic engineering of therapeutic cells
Cell-carrying biomaterials for immune engineering
Biological effects of nanomaterials on cells for regenerative medicine applications
Nanoparticles in imaging and tracing of cells

Dr. Ana Isabel Flores
Dr. Juan Luis Paris
Dr. Paz de la Torre
Guest Editors

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Keywords

nanoparticles
biomaterials
mesenchymal stem cells
cell therapy
nanomedicine
nanotechnology
regenerative medicine
scaffolds

Published Papers (10 papers)

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Research

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18 pages, 6299 KiB

Open AccessArticle

Etched 3D-Printed Polycaprolactone Constructs Functionalized with Reduced Graphene Oxide for Enhanced Attachment of Dental Pulp-Derived Stem Cells

by Austin J. Bow, Thomas J. Masi and Madhu S. Dhar

Pharmaceutics 2021, 13(12), 2146; https://doi.org/10.3390/pharmaceutics13122146 - 13 Dec 2021

Cited by 6 | Viewed by 2555

Abstract

A core challenge in the field of tissue engineering is the ability to establish pipeline workflows for the design and characterization of scaffold technologies with clinically translatable attributes. The parallel development of biomaterials and stem cell populations represents a self-sufficient and streamlined approach for establishing such a pipeline. In the current study, rat dental pulp stem cell (rDPSC) populations were established to assess functionalized polycaprolactone (PCL) constructs. Initial optimization and characterization of rDPSC extraction and culture conditions confirmed that cell populations were readily expandable and demonstrated surface markers associated with multi-potency. Subset populations were transduced to express DsRed fluorescent protein as a mechanism of tracking both cells and cell-derived extracellular matrix content on complex scaffold architecture. Thermoplastic constructs included reduced graphene oxide (rGO) as an additive to promote cellular attachment and were further modified by surface etching a weak acetic acid solution to roughen surface topographical features, which was observed to dramatically improve cell surface coverage in vitro. Based on these data, the modified rGO-functionalized PCL constructs represent a versatile platform for bone tissue engineering, capable of being applied as a standalone matrix or in conjunction with bio-active payloads such as DPSCs or other bio-inks. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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14 pages, 2137 KiB

Open AccessArticle

Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model

by Claudia Báez-Díaz, Virginia Blanco-Blázquez, Francisco Miguel Sánchez-Margallo, Esther López, Helena Martín, Albert Espona-Noguera, Javier G. Casado, Jesús Ciriza, José Luis Pedraz and Verónica Crisóstomo

Pharmaceutics 2021, 13(11), 1824; https://doi.org/10.3390/pharmaceutics13111824 - 01 Nov 2021

Cited by 1 | Viewed by 2412

Abstract

The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-l-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area. We aimed to evaluate IP therapy using a saline vehicle as a control (CON), a dose of 30 × 10⁶ CDCs (CDCs) or APA microcapsules containing 30 × 10⁶ CDCs (APA-CDCs) at 72 h in a porcine AMI model. Magnetic resonance imaging (MRI) was used to determine the left ventricular ejection fraction (LVEF), infarct size (IS), and indexed end diastolic and systolic volumes (EDVi; ESVi) pre- and 10 weeks post-injection. Programmed electrical stimulation (PES) was performed to test arrhythmia inducibility before euthanasia. Histopathological analysis was carried out afterwards. The IP infusion was successful in all animals. At 10 weeks, MRI revealed significantly higher LVEF in the APA-CDC group compared with CON. No significant differences were observed among groups in IS, EDVi, ESVi, PES and histopathological analyses. In conclusion, the IP injection of CDCs (microencapsulated or not) was feasible and safe 72 h post-AMI in the porcine model. Moreover, CDCs APA encapsulation could have a beneficial effect on cardiac function, reflected by a higher LVEF at 10 weeks. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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10 pages, 2324 KiB

Open AccessArticle

Sonazoid-Conjugated Natural Killer Cells for Tumor Therapy and Real-Time Visualization by Ultrasound Imaging

by Hyeong-Woo Song, Han-Sol Lee, Seok-Jae Kim, Ho Yong Kim, You Hee Choi, Byungjeon Kang, Chang-Sei Kim, Jong-Oh Park and Eunpyo Choi

Pharmaceutics 2021, 13(10), 1689; https://doi.org/10.3390/pharmaceutics13101689 - 15 Oct 2021

Cited by 12 | Viewed by 2317

Abstract

Various cell therapy strategies, including chimeric antigen receptor-expressing T or natural killer (NK) cells and cell-mediated drug delivery, have been developed for tumor eradication. However, the efficiency of these strategies against solid tumors remains unclear. We hypothesized that real-time control and visualization of therapeutic cells, such as NK cells, would improve their therapeutic efficacy against solid tumors. In this study, we engineered Sonazoid microbubble-conjugated NK (NK_Sona) cells and demonstrated that they were detectable by ultrasound imaging in real-time and maintained their functions. The Sonazoid microbubbles on the cell membrane did not affect the cytotoxicity and viability of the NK cells in vitro. Additionally, the NK_Sona cells could be visualized by ultrasound imaging and inhibited tumor growth in vivo. Taken together, our findings demonstrate the feasibility of this new approach in the use of therapeutic cells, such as NK cells, against solid tumors. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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18 pages, 6927 KiB

Open AccessArticle

Quantifying Cytosolic Cytochrome c Concentration Using Carbon Quantum Dots as a Powerful Method for Apoptosis Detection

by Cristian Silviu Moldovan, Anca Onaciu, Valentin Toma, Radu Marginean, Alin Moldovan, Adrian Bogdan Tigu, Gabriela Fabiola Stiufiuc, Constantin Mihai Lucaciu and Rares Ionut Stiufiuc

Pharmaceutics 2021, 13(10), 1556; https://doi.org/10.3390/pharmaceutics13101556 - 25 Sep 2021

Cited by 6 | Viewed by 2504

Abstract

Background: Cytochrome c (Cyt c) is a key biomarker for early apoptosis, and many methods were designed to detect its release from mitochondria. For a proper evaluation of these programed cell death mechanisms, fluorescent nanoparticles are excellent candidates due to their valuable optical properties. Among all classes of nanoparticles developed thus far, carbon-based quantum dots bring qualitative and efficient imaging strategies for biomedical applications as a consequence of their biocompatibility and low cytotoxicity. Methods: In this study, we synthesized carbon quantum dots smaller than 5 nm from sodium citrate and polyethylene imine. These nanoparticles were rigorously characterized, and their quenching capacity in apoptotic events was assessed in A549 cells treated with staurosporine and etoposide. For the evaluation of Cyt c release, a phenomenon directly correlated with apoptotic events, we ran a semiquantitative analysis using confocal laser scanning microscopy. Results: Carbon quantum dots were synthesized and were successfully employed for Cyt c detection by means of fluorescence microscopy. Significant drops in fluorescence intensity were observed in the case of cells treated with apoptosis-inducing therapeutic compounds compared to untreated cells, confirming Cyt c release from mitochondria to cytosol. Conclusion: Considering these results, we strongly believe this method can contribute to an indirect in vitro evaluation of apoptosis. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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13 pages, 2510 KiB

Open AccessArticle

Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy

by Ascensión López-Díaz de Cerio, Iñigo Perez-Estenaga, Susana Inoges, Gloria Abizanda, Juan José Gavira, Eduardo Larequi, Enrique Andreu, Saray Rodriguez, Ana Gloria Gil, Verónica Crisostomo, Francisco Miguel Sanchez-Margallo, Javier Bermejo, Blanca Jauregui, Lluis Quintana, Francisco Fernández-Avilés, Beatriz Pelacho and Felipe Prósper

Pharmaceutics 2021, 13(8), 1269; https://doi.org/10.3390/pharmaceutics13081269 - 17 Aug 2021

Cited by 4 | Viewed by 2087

Abstract

The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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Review

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18 pages, 1677 KiB

Open AccessReview

Bacteria as Nanoparticle Carriers for Immunotherapy in Oncology

by Víctor M. Moreno and Alejandro Baeza

Pharmaceutics 2022, 14(4), 784; https://doi.org/10.3390/pharmaceutics14040784 - 03 Apr 2022

Cited by 4 | Viewed by 2781

Abstract

The use of nanocarriers to deliver antitumor agents to solid tumors must overcome biological barriers in order to provide effective clinical responses. Once within the tumor, a nanocarrier should navigate into a dense extracellular matrix, overcoming intratumoral pressure to push it out of the diseased tissue. In recent years, a paradigm change has been proposed, shifting the target of nanomedicine from the tumoral cells to the immune system, in order to exploit the natural ability of this system to capture and interact with nanometric moieties. Thus, nanocarriers have been engineered to interact with immune cells, with the aim of triggering specific antitumor responses. The use of bacteria as nanoparticle carriers has been proposed as a valuable strategy to improve both the accumulation of nanomedicines in solid tumors and their penetration into the malignancy. These microorganisms are capable of propelling themselves into biological environments and navigating through the tumor, guided by the presence of specific molecules secreted by the diseased tissue. These capacities, in addition to the natural immunogenic nature of bacteria, can be exploited to design more effective immunotherapies that yield potent synergistic effects to induce efficient and selective immune responses that lead to the complete eradication of the tumor. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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18 pages, 2179 KiB

Open AccessReview

Recent Advances in the Application of Mesenchymal Stem Cell-Derived Exosomes for Cardiovascular and Neurodegenerative Disease Therapies

by Zhimin Yang, Yanyu Li and Zihua Wang

Pharmaceutics 2022, 14(3), 618; https://doi.org/10.3390/pharmaceutics14030618 - 11 Mar 2022

Cited by 18 | Viewed by 3644

Abstract

Exosomes are naturally occurring nanoscale vesicles that are released and received by almost all cells in the body. Exosomes can be transferred between cells and contain various molecular constitutes closely related to their origin and function, including proteins, lipids, and RNAs. The importance of exosomes in cellular communication makes them important vectors for delivering a variety of drugs throughout the body. Exosomes are ubiquitous in the circulatory system and can reach the site of injury or disease through a variety of biological barriers. Due to its unique structure and rich inclusions, it can be used for the diagnosis and treatment of diseases. Mesenchymal stem-cell-derived exosomes (MSCs-Exo) inherit the physiological functions of MSCs, including repairing and regenerating tissues, suppressing inflammatory responses, and regulating the body’s immunity; therefore, MSCs-Exo can be used as a natural drug delivery carrier with therapeutic effects, and has been increasingly used in the treatment of cardiovascular diseases and neurodegenerative diseases. Here, we summarize the research progress of MSCs-Exo as drug delivery vectors and their application for various drug deliveries, providing ideas and references for the study of MSCs-Exo in recent years. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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30 pages, 1320 KiB

Open AccessEditor’s ChoiceReview

A Narrative Review of Cell-Based Approaches for Cranial Bone Regeneration

by Maria I. Falguera Uceda, Silvia Sánchez-Casanova, Clara Escudero-Duch and Nuria Vilaboa

Pharmaceutics 2022, 14(1), 132; https://doi.org/10.3390/pharmaceutics14010132 - 05 Jan 2022

Cited by 10 | Viewed by 3025

Abstract

Current cranial repair techniques combine the use of autologous bone grafts and biomaterials. In addition to their association with harvesting morbidity, autografts are often limited by insufficient quantity of bone stock. Biomaterials lead to better outcomes, but their effectiveness is often compromised by the unpredictable lack of integration and structural failure. Bone tissue engineering offers the promising alternative of generating constructs composed of instructive biomaterials including cells or cell-secreted products, which could enhance the outcome of reconstructive treatments. This review focuses on cell-based approaches with potential to regenerate calvarial bone defects, including human studies and preclinical research. Further, we discuss strategies to deliver extracellular matrix, conditioned media and extracellular vesicles derived from cell cultures. Recent advances in 3D printing and bioprinting techniques that appear to be promising for cranial reconstruction are also discussed. Finally, we review cell-based gene therapy approaches, covering both unregulated and regulated gene switches that can create spatiotemporal patterns of transgenic therapeutic molecules. In summary, this review provides an overview of the current developments in cell-based strategies with potential to enhance the surgical armamentarium for regenerating cranial vault defects. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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20 pages, 1985 KiB

Open AccessReview

New Therapeutic Approaches for Allergy: A Review of Cell Therapy and Bio- or Nano-Material-Based Strategies

by Juan L. Paris, Paz de la Torre and Ana I. Flores

Pharmaceutics 2021, 13(12), 2149; https://doi.org/10.3390/pharmaceutics13122149 - 14 Dec 2021

Cited by 6 | Viewed by 2918

Abstract

Allergy constitutes a major health issue due to its large prevalence. The established therapeutic approaches (allergen avoidance, antihistamines, and corticosteroids) do not address the underlying causes of the pathology, highlighting the need for other long-term treatment options. Antigen-specific immunotherapy enables the long-term control of allergic diseases by promoting immunological tolerance to the allergen. However, efficacious immunotherapies are not available for all possible allergens, and the risk of undesired reactions during therapy remains a concern, especially in patients with severe allergic reactions. In this context, two types of therapeutic strategies appear especially promising for the future in the context of allergy: cell therapy and bio- or nano-material-based therapy. In this review, the main strategies developed this far in these two types of strategies are discussed, with several examples illustrating the different approaches. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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28 pages, 3299 KiB

Open AccessReview

Combination of Nanomaterials in Cell-Based Drug Delivery Systems for Cancer Treatment

by Lu Tang, Shun He, Yue Yin, Hening Liu, Jingyi Hu, Jie Cheng and Wei Wang

Pharmaceutics 2021, 13(11), 1888; https://doi.org/10.3390/pharmaceutics13111888 - 08 Nov 2021

Cited by 28 | Viewed by 3706

Abstract

Cell-based drug delivery systems have shown tremendous advantages in cancer treatment due to their distinctive properties. For instance, delivery of therapeutics using tumor-tropic cells like neutrophils, lymphocytes and mesenchymal stem cells can achieve specific tumor targeting due to the “Trojan Horse” effect. Other circulatory cells like erythrocytes and platelets can greatly improve the circulation time of nanoparticles due to their innate long circulation property. Adipocytes, especially cancer-associated adipocytes, play key roles in tumor development and metabolism, therefore, adipocytes are regarded as promising bio-derived nanoplatforms for anticancer targeted drug delivery. Nanomaterials are important participants in cell-based drug delivery because of their unique physicochemical characteristics. Therefore, the integration of various nanomaterials with different cell types will endow the constructed delivery systems with many attractive properties due to the merits of both. In this review, a number of strategies based on nanomaterial-involved cell-mediated drug delivery systems for cancer treatment will be summarized. This review discusses how nanomaterials can be a benefit to cell-based therapies and how cell-derived carriers overcome the limitations of nanomaterials, which highlights recent advancements and specific biomedical applications based on nanomaterial-mediated, cell-based drug delivery systems. Full article

(This article belongs to the Special Issue Application of Nano- and Bio-materials in Cell-Based Therapy)

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