Photo-Cross-Linkable Human Albumin Colloidal Gels Facilitate In Vivo Vascular Integration for Regenerative Medicine

AbstractRecently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

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Cell Therapy and Bioengineering in Experimental Liver Regenerative Medicine: In Vivo Injury Models and Grafting Strategies

Current Transplantation Reports ◽

10.1007/s40472-021-00325-2 ◽

2021 ◽

Author(s):

G. Amato ◽

T. Saleh ◽

G. Carpino ◽

E. Gaudio ◽

D. Alvaro ◽

...

Keyword(s):

Regenerative Medicine ◽

Cell Therapy ◽

Cell Delivery ◽

Effective Strategies ◽

Multiple Strategies ◽

End Stage ◽

Therapy Strategies ◽

Injury Models ◽

Experimental Liver

Abstract Purpose of Review To describe experimental liver injury models used in regenerative medicine, cell therapy strategies to repopulate damaged livers and the efficacy of liver bioengineering. Recent Findings Several animal models have been developed to study different liver conditions. Multiple strategies and modified protocols of cell delivery have been also reported. Furthermore, using bioengineered liver scaffolds has shown promising results that could help in generating a highly functional cell delivery system and/or a whole transplantable liver. Summary To optimize the most effective strategies for liver cell therapy, further studies are required to compare among the performed strategies in the literature and/or innovate a novel modifying technique to overcome the potential limitations. Coating of cells with polymers, decellularized scaffolds, or microbeads could be the most appropriate solution to improve cellular efficacy. Besides, overcoming the problems of liver bioengineering may offer a radical treatment for end-stage liver diseases.

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Reversal of senescence-associated beta-galactosidase expression during in vitro three-dimensional tissue-engineering of human chondrocytes in a polymer scaffold

Scientific Reports ◽

10.1038/s41598-021-93607-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shojiro Katoh ◽

Atsuki Fujimaru ◽

Masaru Iwasaki ◽

Hiroshi Yoshioka ◽

Rajappa Senthilkumar ◽

...

Keyword(s):

Regenerative Medicine ◽

Replicative Senescence ◽

Cultured Cells ◽

Three Dimensional ◽

Human Chondrocytes ◽

Cartilage Tissue ◽

Optimal Method ◽

Beta Galactosidase

AbstractRegenerative medicine applications require cells that are not inflicted with senescence after in vitro culture for an optimal in vivo outcome. Methods to overcome replicative senescence include genomic modifications which have their own disadvantages. We have evaluated a three-dimensional (3D) thermo-reversible gelation polymer (TGP) matrix environment for its capabilities to reverse cellular senescence. The expression of senescence-associated beta-galactosidase (SA-βgal) by human chondrocytes from osteoarthritis-affected cartilage tissue, grown in a conventional two-dimensional (2D) monolayer culture versus in 3D-TGP were compared. In 2D, the cells de-differentiated into fibroblasts, expressed higher SA-βgal and started degenerating at 25 days. SA-βgal levels decreased when the chondrocytes were transferred from the 2D to the 3D-TGP culture, with cells exhibiting a tissue-like growth until 42–45 days. Other senescence associated markers such as p16INK4a and p21 were also expressed only in 2D cultured cells but not in 3D-TGP tissue engineered cartilage. This is a first-of-its-kind report of a chemically synthesized and reproducible in vitro environment yielding an advantageous reversal of aging of human chondrocytes without any genomic modifications. The method is worth consideration as an optimal method for growing cells for regenerative medicine applications.

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Regenerative Medicine and Angiogenesis; Challenges and Opportunities

Advanced Pharmaceutical Bulletin ◽

10.34172/apb.2020.061 ◽

2020 ◽

Vol 10 (4) ◽

pp. 490-501

Author(s):

Mozhgan Jahani ◽

Davood Rezazadeh ◽

Parisa Mohammadi ◽

Amir Abdolmaleki ◽

Amir Norooznezhad ◽

...

Keyword(s):

Regenerative Medicine ◽

Large Scale ◽

Diffusion Limit ◽

Blood Vessel Development ◽

Engineering Technique ◽

Challenges And Opportunities ◽

Vessel Development ◽

Tissue Engineering Technique

Blood vessel development is one of the most prominent steps in regenerative medicine due tothe restoration of blood flow to the ischemic tissues and providing the rapid vascularizationin clinical-sized tissue-engineered grafts. However, currently tissue engineering technique isrestricted because of the inadequate in vitro/in vivo tissue vascularization. Some challenges likeas transportation in large scale, distribution of the nutrients and poor oxygen diffusion limit theprogression of vessels in smaller than clinically relevant dimensions as well in vivo integration.In this regard, the scholars attempted to promote the vascularization process relied on the stemcells (SCs), growth factors as well as exosomes and interactions of biomaterials with all of themto enable the emergence of ideal microenvironment which is needed for treatment of unhealthyorgans or tissue regeneration and formation of new blood vessels. Thus, in the present reviewwe aim to describe these approaches, advances, obstacles and opportunities as well as theirapplication in regeneration of heart as a prominent angiogenesis-dependent organ.

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BioMEMS Technologies for Regenerative Medicine

MRS Proceedings ◽

10.1557/proc-1139-gg02-01 ◽

2008 ◽

Vol 1139 ◽

Cited By ~ 3

Author(s):

Jeffrey T. Borenstein

Keyword(s):

Drug Delivery ◽

Regenerative Medicine ◽

Drug Delivery Systems ◽

Ex Vivo ◽

Delivery Systems ◽

Organ Shortage ◽

Engineered Tissues ◽

Drug Concentrations

AbstractThe emergence of BioMEMS fabrication technologies such as soft lithography, micromolding and assembly of 3D structures, and biodegradable microfluidics, are already making significant contributions to the field of regenerative medicine. Over the past decade, BioMEMS have evolved from early silicon laboratory devices to polymer-based structures and even biodegradable constructs suitable for a range of ex vivo and in vivo applications. These systems are still in the early stages of development, but the long-term potential of the technology promises to enable breakthroughs in health care challenges ranging from the systemic toxicity of drugs to the organ shortage. Ex vivo systems for organ assist applications are emerging for the liver, kidney and lung, and the precision and scalability of BioMEMS fabrication techniques offer the promise of dramatic improvements in device performance and patient outcomes.Ultimately, the greatest benefit from BioMEMS technologies will be realized in applications for implantable devices and systems. Principal advantages include the extreme levels of achievable miniaturization, integration of multiple functions such as delivery, sensing and closed loop control, and the ability of precision microscale and nanoscale features to reproduce the cellular microenvironment to sustain long-term functionality of engineered tissues. Drug delivery systems based on BioMEMS technologies are enabling local, programmable control over drug concentrations and pharmacokinetics for a broad spectrum of conditions and target organs. BioMEMS fabrication methods are also being applied to the development of engineered tissues for applications such as wound healing, microvascular networks and bioartificial organs. Here we review recent progress in BioMEMS-based drug delivery systems, engineered tissue constructs and organ assist devices for a range of ex vivo and in vivo applications in regenerative medicine.

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Melt Processed Polymer Blends for Potential Regenerative Medicine Applications

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.679.92 ◽

2014 ◽

Vol 679 ◽

pp. 92-100

Author(s):

Elaine Kenny ◽

Declan M. Devine ◽

Clement L. Higginbotham ◽

Luke M. Geever

Keyword(s):

Molecular Weight ◽

Differential Scanning Calorimetry ◽

Regenerative Medicine ◽

Polyethylene Oxide ◽

Melt Flow Index ◽

Flow Index ◽

Biodegradable Implants ◽

Scanning Calorimetry ◽

Breakdown Rate

There is an urgent and unmet requirement for biocompatible and biodegradable implants that gradually resorb when implanted in vivo. This study examines the potential of melt extruded thermoplastics polyethylene oxide (PEO) and polycaprolactone (PCL) in the area of regenerative medicine. Various ratios of PEO and PCL were melt blended and analysed in order to obtain an optimised breakdown rate. Subsequently the effect of varying the molecular weight of PCL using a constant molecular weight PEO was also examined. Samples were characterised using melt flow index (MFI), differential scanning calorimetry (DSC) and breakdown analysis. It was found that by altering both the concentrations of PEO/PCL and the molecular weight of PCL, melt viscosity, breakdown rate and thermal properties could be modulated to produce potential implant materials with a tailored breakdown rate.

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Design and characterization of an in vivo injectable hydrogel with effervescently generated porosity for regenerative medicine applications

Acta Biomaterialia ◽

10.1016/j.actbio.2021.11.036 ◽

2021 ◽

Author(s):

Louise Griveau ◽

Marianne Lafont ◽

Héloïse le Goff ◽

Clémence Drouglazet ◽

Baptiste Robbiani ◽

...

Keyword(s):

Regenerative Medicine ◽

Injectable Hydrogel

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Probing Vasculature by In Vivo Phage Display for Target Organ-Specific Delivery in Regenerative Medicine

Reference Series in Biomedical Engineering ◽

10.1007/978-3-319-54586-8_21 ◽

2021 ◽

pp. 179-204

Author(s):

Toini Pemmari ◽

Tiia Koho ◽

Tero A. H. Järvinen

Keyword(s):

Regenerative Medicine ◽

Phage Display ◽

Target Organ ◽

Organ Specific ◽

In Vivo Phage Display

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Advances in Pluripotent Stem Cells: History, Mechanisms, Technologies, and Applications

Stem Cell Reviews and Reports ◽

10.1007/s12015-019-09935-x ◽

2019 ◽

Vol 16 (1) ◽

pp. 3-32 ◽

Cited By ~ 22

Author(s):

Gele Liu ◽

Brian T. David ◽

Matthew Trawczynski ◽

Richard G. Fessler

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Regenerative Medicine ◽

Pluripotent Stem Cells ◽

Cell Biology ◽

Ethical Issues ◽

Three Dimensional ◽

Future Research ◽

Cell Technology

AbstractOver the past 20 years, and particularly in the last decade, significant developmental milestones have driven basic, translational, and clinical advances in the field of stem cell and regenerative medicine. In this article, we provide a systemic overview of the major recent discoveries in this exciting and rapidly developing field. We begin by discussing experimental advances in the generation and differentiation of pluripotent stem cells (PSCs), next moving to the maintenance of stem cells in different culture types, and finishing with a discussion of three-dimensional (3D) cell technology and future stem cell applications. Specifically, we highlight the following crucial domains: 1) sources of pluripotent cells; 2) next-generation in vivo direct reprogramming technology; 3) cell types derived from PSCs and the influence of genetic memory; 4) induction of pluripotency with genomic modifications; 5) construction of vectors with reprogramming factor combinations; 6) enhancing pluripotency with small molecules and genetic signaling pathways; 7) induction of cell reprogramming by RNA signaling; 8) induction and enhancement of pluripotency with chemicals; 9) maintenance of pluripotency and genomic stability in induced pluripotent stem cells (iPSCs); 10) feeder-free and xenon-free culture environments; 11) biomaterial applications in stem cell biology; 12) three-dimensional (3D) cell technology; 13) 3D bioprinting; 14) downstream stem cell applications; and 15) current ethical issues in stem cell and regenerative medicine. This review, encompassing the fundamental concepts of regenerative medicine, is intended to provide a comprehensive portrait of important progress in stem cell research and development. Innovative technologies and real-world applications are emphasized for readers interested in the exciting, promising, and challenging field of stem cells and those seeking guidance in planning future research direction.

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The application of resveratrol to mesenchymal stromal cell-based regenerative medicine

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1412-9 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Chenxia Hu ◽

Lanjuan Li

Keyword(s):

Regenerative Medicine ◽

Tissue Injury ◽

Lineage Commitment ◽

Root Extract ◽

Therapeutic Effects ◽

Aging Effects ◽

Chronic Injury ◽

Self Renewal

Abstract Currently, the transplantation of mesenchymal stromal cells (MSCs) has emerged as an effective strategy to protect against tissue and organ injury. MSC transplantation also serves as a promising therapy for regenerative medicine, while poor engraftment and limited survival rates are major obstacles for its clinical application. Although multiple studies have focused on investigating chemicals to improve MSC stemness and differentiation in vitro and in vivo, there is still a shortage of effective and safe agents for MSC-based regenerative medicine. Resveratrol (RSV), a nonflavonoid polyphenol phytoalexin with a stilbene structure, was first identified in the root extract of white hellebore and is also found in the roots of Polygonum cuspidatum, and it is widely used in traditional Chinese medicine. RSV is a natural agent that possesses great therapeutic potential for protecting against acute or chronic injury in multiple tissues as a result of its antioxidative, anti-inflammatory, and anti-cancer properties. According to its demonstrated properties, RSV may improve the therapeutic effects of MSCs via enhancing their survival, self-renewal, lineage commitment, and anti-aging effects. In this review, we concluded that RSV significantly improved the preventive and therapeutic effects of MSCs against multiple diseases. We also described the underlying mechanisms of the effects of RSV on the survival, self-renewal, and lineage commitment of MSCs in vitro and in vivo. Upon further clarification of the potential mechanisms of the effects of RSV on MSC-based therapy, MSCs may be able to be more widely used in regenerative medicine to promote recovery from tissue injury.

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