Use of l-pNIPAM hydrogel as a 3D-scaffold for intestinal crypts and stem cell tissue engineering

Muscle and nerve tissue damage can elicit a significant loss of function and poses as a burden for patients and healthcare providers. Even for tissues, such as the peripheral nerve and skeletal muscle, that harbor significant regenerative capacity, innate regenerative processes often lead to less than optimal recovery and residual loss of function. The reasons for poor regeneration include significant cell damage secondary to oxidative stress, poor recruitment of resident stem cells, and an unfavorable microenvironment for tissue regeneration. Stem cell-based therapy was once thought as a potential therapy in tissue regeneration, due to its self-renewal and multipotent capabilities. Early advocates for cellular-based therapy pointed to the pluripotent nature of stem cells, thus eluding to its ability to differentiate into resident cells as the source of its regenerative capability. However, increasing evidence has revealed a lack of engraftment and differentiation of stem cells, thereby pointing to stem cell paracrine activity as being responsible for its regenerative potential. Stem cell-conditioned media houses biomolecular factors that portray significant regenerative potential. Amniotic-derived stem cell-conditioned media (AFS-CM) has been of particular interest because of its ease of allocation and in vitro culture. The purpose of this review is to report the results of studies that assess the role of AFS-CM for nerve and muscle conditions. In this review, we will cover the effects of AFS-CM on cellular pathways, genes, and protein expression for different nerve and muscle cell types.

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Regulation and Directing Stem Cell Fate by Tissue Engineering Functional Microenvironments: Scaffold Physical and Chemical Cues

Stem Cells International ◽

10.1155/2019/2180925 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 8

Author(s):

Fei Xing ◽

Lang Li ◽

Changchun Zhou ◽

Cheng Long ◽

Lina Wu ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Stem Cell ◽

Growth Factors ◽

Cell Fate ◽

Chemical Cues ◽

Physical Factors ◽

Stem Cell Fate ◽

Physical And Chemical

It is well known that stem cells reside within tissue engineering functional microenvironments that physically localize them and direct their stem cell fate. Recent efforts in the development of more complex and engineered scaffold technologies, together with new understanding of stem cell behavior in vitro, have provided a new impetus to study regulation and directing stem cell fate. A variety of tissue engineering technologies have been developed to regulate the fate of stem cells. Traditional methods to change the fate of stem cells are adding growth factors or some signaling pathways. In recent years, many studies have revealed that the geometrical microenvironment played an essential role in regulating the fate of stem cells, and the physical factors of scaffolds including mechanical properties, pore sizes, porosity, surface stiffness, three-dimensional structures, and mechanical stimulation may affect the fate of stem cells. Chemical factors such as cell-adhesive ligands and exogenous growth factors would also regulate the fate of stem cells. Understanding how these physical and chemical cues affect the fate of stem cells is essential for building more complex and controlled scaffolds for directing stem cell fate.

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Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting

Scientific Reports ◽

10.1038/s41598-020-73188-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Guillermo Bauza ◽

Anna Pasto ◽

Patrick Mcculloch ◽

David Lintner ◽

Ava Brozovich ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Articular Cartilage ◽

Cartilage Repair ◽

Adipogenic Differentiation ◽

3D Culture ◽

Cell Populations ◽

Stem Cell Markers ◽

3D Scaffold

Abstract Cartilage repair in osteoarthritic patients remains a challenge. Identifying resident or donor stem/progenitor cell populations is crucial for augmenting the low intrinsic repair potential of hyaline cartilage. Furthermore, mediating the interaction between these cells and the local immunogenic environment is thought to be critical for long term repair and regeneration. In this study we propose articular cartilage progenitor/stem cells (CPSC) as a valid alternative to bone marrow-derived mesenchymal stem cells (BMMSC) for cartilage repair strategies after trauma. Similar to BMMSC, CPSC isolated from osteoarthritic patients express stem cell markers and have chondrogenic, osteogenic, and adipogenic differentiation ability. In an in vitro 2D setting, CPSC show higher expression of SPP1 and LEP, markers of osteogenic and adipogenic differentiation, respectively. CPSC also display a higher commitment toward chondrogenesis as demonstrated by a higher expression of ACAN. BMMSC and CPSC were cultured in vitro using a previously established collagen-chondroitin sulfate 3D scaffold. The scaffold mimics the cartilage niche, allowing both cell populations to maintain their stem cell features and improve their immunosuppressive potential, demonstrated by the inhibition of activated PBMC proliferation in a co-culture setting. As a result, this study suggests articular cartilage derived-CPSC can be used as a novel tool for cellular and acellular regenerative medicine approaches for osteoarthritis (OA). In addition, the benefit of utilizing a biomimetic acellular scaffold as an advanced 3D culture system to more accurately mimic the physiological environment is demonstrated.

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Immunomodulatory Functions of Mesenchymal Stem Cells in Tissue Engineering

Stem Cells International ◽

10.1155/2019/9671206 ◽

2019 ◽

Vol 2019 ◽

pp. 1-18 ◽

Cited By ~ 14

Author(s):

Haojiang Li ◽

Shi Shen ◽

Haitao Fu ◽

Zhenyong Wang ◽

Xu Li ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Tissue Regeneration ◽

Tissue Damage ◽

Material Selection ◽

Immune Microenvironment ◽

Chronic Injury ◽

Research Fields

The inflammatory response to chronic injury affects tissue regeneration and has become an important factor influencing the prognosis of patients. In previous stem cell treatments, it was revealed that stem cells not only have the ability for direct differentiation or regeneration in chronic tissue damage but also have a regulatory effect on the immune microenvironment. Stem cells can regulate the immune microenvironment during tissue repair and provide a good “soil” for tissue regeneration. In the current study, the regulation of immune cells by mesenchymal stem cells (MSCs) in the local tissue microenvironment and the tissue damage repair mechanisms are revealed. The application of the concepts of “seed” and “soil” has opened up new research avenues for regenerative medicine. Tissue engineering (TE) technology has been used in multiple tissues and organs using its biomimetic and cellular cell abilities, and scaffolds are now seen as an important part of building seed cell microenvironments. The effect of tissue engineering techniques on stem cell immune regulation is related to the shape and structure of the scaffold, the preinflammatory microenvironment constructed by the implanted scaffold, and the material selection of the scaffold. In the application of scaffold, stem cell technology has important applications in cartilage, bone, heart, and liver and other research fields. In this review, we separately explore the mechanism of MSCs in different tissue and organs through immunoregulation for tissue regeneration and MSC combined with 3D scaffolds to promote MSC immunoregulation to repair damaged tissues.

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Prospect of Stem Cells in Bone Tissue Engineering: A Review

Stem Cells International ◽

10.1155/2016/6180487 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 88

Author(s):

Azizeh-Mitra Yousefi ◽

Paul F. James ◽

Rosa Akbarzadeh ◽

Aswati Subramanian ◽

Conor Flavin ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Cell Types ◽

3D Scaffold ◽

Stem Cell Source ◽

Induced Pluripotent

Mesenchymal stem cells (MSCs) have been the subject of many studies in recent years, ranging from basic science that looks into MSCs properties to studies that aim for developing bioengineered tissues and organs. Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) have been the focus of most studies due to the inherent potential of these cells to differentiate into various cell types. Although, the discovery of induced pluripotent stem cells (iPSCs) represents a paradigm shift in our understanding of cellular differentiation. These cells are another attractive stem cell source because of their ability to be reprogramed, allowing the generation of multiple cell types from a single cell. This paper briefly covers various types of stem cell sources that have been used for tissue engineering applications, with a focus on bone regeneration. Then, an overview of some recent studies making use of MSC-seeded 3D scaffold systems for bone tissue engineering has been presented. The emphasis has been placed on the reported scaffold properties that tend to improve MSCs adhesion, proliferation, and osteogenic differentiation outcomes.

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The Effect of Diabetes Mellitus on IGF Axis and Stem Cell Mediated Regeneration of the Periodontium

Bioengineering ◽

10.3390/bioengineering8120202 ◽

2021 ◽

Vol 8 (12) ◽

pp. 202

Author(s):

Nancy M. S. Hussein ◽

Josie L. Meade ◽

Hemant Pandit ◽

Elena Jones ◽

Reem El-Gendy

Keyword(s):

Diabetes Mellitus ◽

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Tissue Regeneration ◽

Diabetic Patients ◽

Periodontal Tissue ◽

Signalling Molecules ◽

Periodontal Tissues

Periodontitis and diabetes mellitus (DM) are two of the most common and challenging health problems worldwide and they affect each other mutually and adversely. Current periodontal therapies have unpredictable outcome in diabetic patients. Periodontal tissue engineering is a challenging but promising approach that aims at restoring periodontal tissues using one or all of the following: stem cells, signalling molecules and scaffolds. Mesenchymal stem cells (MSCs) and insulin-like growth factor (IGF) represent ideal examples of stem cells and signalling molecules. This review outlines the most recent updates in characterizing MSCs isolated from diabetics to fully understand why diabetics are more prone to periodontitis that theoretically reflect the impaired regenerative capabilities of their native stem cells. This characterisation is of utmost importance to enhance autologous stem cells based tissue regeneration in diabetic patients using both MSCs and members of IGF axis.

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Intestinal Organoids—Current and Future Applications

10.20944/preprints201608.0090.v1 ◽

2016 ◽

Author(s):

Andre M. C. Meneses ◽

Kerstin Schneeberger ◽

Hedwig S. Kruitwagen ◽

Louis C. Penning ◽

Frank G. van Steenbeek ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Pluripotent Stem Cells ◽

Disease Modeling ◽

Three Dimensional ◽

Intestinal Stem Cells ◽

Complex Structures ◽

Technical Advances ◽

Induced Pluripotent

Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from various species, organs and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we report on intestinal stem cells, organoid culture, organoid disease modeling, transplantation, current and future uses of this exciting new insight model to veterinary medicine field.

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Rapid Rapamycin-Only Induced Osteogenic Differentiation of Blood-Derived Stem Cells and Their Adhesion to Natural and Artificial Scaffolds

Stem Cells International ◽

10.1155/2017/2976541 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12

Author(s):

Carpentieri Arianna ◽

Cozzoli Eliana ◽

Acri Flavio ◽

Ranalli Marco ◽

Diedenhofen Giacomo ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Stem Cell ◽

Osteogenic Differentiation ◽

Molecular Mechanisms ◽

Maxillofacial Surgery ◽

Ongoing Research ◽

Medicine Research ◽

Cell Based Therapy

Stem cells are a centerpiece of regenerative medicine research, and the recent development of adult stem cell-based therapy systems has vigorously expanded the scope and depth of this scientific field. The regeneration of damaged and/or degraded bone tissue in orthopedic, dental, or maxillofacial surgery is one of the main areas where stem cells and their regenerative potential could be used successfully, requiring tissue engineering solutions incorporating an ideal stem cell type paired with the correct mechanical support. Our contribution to this ongoing research provides a new model of in vitro osteogenic differentiation using blood-derived stem cells (BDSCs) and rapamycin, visibly expressing typical osteogenic markers within ten days of treatment. In depth imaging studies allowed us to observe the adhesion, proliferation, and differentiation of BDSCs to both titanium and bone scaffolds. We demonstrate that BDSCs can differentiate towards the osteogenic lineage rapidly, while readily adhering to the scaffolds we exposed them to. Our results show that our model can be a valid tool to study the molecular mechanisms of osteogenesis while tailoring tissue engineering solutions to these new insights.

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The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2116865118 ◽

2022 ◽

Vol 119 (2) ◽

pp. e2116865118

Author(s):

Shiv Shah ◽

Caldon Jayson Esdaille ◽

Maumita Bhattacharjee ◽

Ho-Man Kan ◽

Cato T. Laurencin

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Tissue Regeneration ◽

Therapeutic Strategy ◽

Cartilage Degeneration ◽

Biomechanical Properties ◽

Adipose Derived Stem Cells ◽

Rodent Models

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.

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Mesenchymal stem cells in the dental tissues: perspectives for tissue regeneration

Brazilian Dental Journal ◽

10.1590/s0103-64402011000200001 ◽

2011 ◽

Vol 22 (2) ◽

pp. 91-98 ◽

Cited By ~ 83

Author(s):

Carlos Estrela ◽

Ana Helena Gonçalves de Alencar ◽

Gregory Thomas Kitten ◽

Eneida Franco Vencio ◽

Elisandra Gava

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Tissue Regeneration ◽

Stem Cell Research ◽

Cell Biology ◽

Dental Tissues ◽

New Findings ◽

Dental Stem Cell

In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that range from Alzheimer’s disease to cardiac ischemia and regenerative medicine, like bone or tooth loss. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have been speculated. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental tissues are considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that these stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. In dentistry, stem cell biology and tissue engineering are of great interest since may provide an innovative for generation of clinical material and/or tissue regeneration. Mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, dental papilla, and dental follicle. These stem cells can be isolated and grown under defined tissue culture conditions, and are potential cells for use in tissue engineering, including, dental tissue, nerves and bone regeneration. More recently, another source of stem cell has been successfully generated from human somatic cells into a pluripotent stage, the induced pluripotent stem cells (iPS cells), allowing creation of patient- and disease-specific stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental stem cell an attractive source of mesenchymal stem cells for tissue regeneration. This review describes new findings in the field of dental stem cell research and on their potential use in the tissue regeneration.

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