Damian Jacob Sendler Research On Regenerative Medicine
Damian Sendler: When it comes to immunomodulation, ASCs are considered to be powerful. This means that they are capable of sensing their surroundings and adapting accordingly. Several types of mesenchymal stem cells have been shown to inhibit viral replication and lower viral loads (Rogers et al., 2020). Accordingly, researchers are exploring the feasibility of using ASCs to treat COVID-19 infected individuals. Lung tissue destruction, severe inflammation, and fibrosis development are the most common side effects of COVID-19 infection. Immune cell infiltration may be reduced and injured tissue repaired using MSCs, as Shi and others have shown in early clinical trials with ASC injections (Shi et al., 2021). Leng et al. found that intravenous injection of stem cells in COVID-19 patients with pneumonia decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines such as IL-10, therefore facilitating lung healing in the research participants (Leng et al., 2020).
Damian Jacob Sendler: Treatment of severe COVID-19 patients with autologous or allogeneic ASCs was examined by Gentile and Sterodimas in their research (Gentile and Sterodimas, 2020). By enhancing the pulmonary milieu, ASC infusions promote endogenous healing by inhibiting immune system over-activation. The kind of stem cells, dosage, time interval, and delivery technique need be adjusted for future clinical uses, even if ASCs have demonstrated promising results. As the findings of the current clinical studies of COVID-19 are announced, some of these difficulties may be resolved.
Damian Sendler
Stem cell applications for a wide range of disorders, including cardiovascular, neurological, vascular, diabetes, and inflammation, have been opened up by nanotechnology (Masoudi Asil et al., 2020; Dong et al., 2021; Sarathkumar et al., 2021). Notably, NPs are by-products of ASCs that are released as extracellular vesicles (EVs) (Wang et al., 2009; Dong et al., 2021). Tissue healing may be studied in great detail using NPs produced from ASCs, and these NPs can be used to create a more accurate technique of targeted treatment (Qiu et al., 2018; Dong et al., 2021). Organoids, organ-on-a-chip systems, and lab-grown organs and tissues are all made possible by mixing stem cells with scaffolds.
Dr. Sendler: The extracellular matrix (ECM) and an in vivo-like milieu are necessary for stem cell attachment and proliferation in scaffolds, synthetic or natural, that are employed in tissue engineering applications. There are two types of scaffolds: synthetic (polyethers, polyethylene glycol, and polylactic acid) and natural (collagens, fibrins, gelatins, vitronectin, alginate hyaluronic acid, and decellularized materials (DAT)) (Sadeghi-Ataabadi et al., 2017; Vinson et al., 2017; Kook et al., 2018; Mohiuddin O. A., 2019; Collins et al., 2020; O'Donnell, 2020). Cell adhesion, proliferation, and differentiation; fibrosity and stiffness; biocompatibility with the tissue and biodegradability with a minimum level of toxicity or inflammation in vivo are the primary properties of the scaffolds (Dhandayuthapani et al., 2011; Reddy et al., 2021). The capacity of ASCs to attach, move, and differentiate into particular cell lines has been proven in a number of experiments with 3D scaffolds.
Damian Jacob Markiewicz Sendler:The capacity of stem cells to differentiate may be influenced by the nanomaterial employed in the creation of ASC scaffolds. Growth factors (such as VEGF, bFGF, and TGF-) may be efficiently incorporated into a scaffold in addition to the ECM-ASC interactions in order to improve the therapeutic potential by boosting stem cell proliferation and differentiation (Howard et al., 2008; Sell et al., 2011; Sadeghi-Ataabadi et al., 2017). The ability of ASCs planted on PRP fibrin enriched scaffolds to repair cartilage and regenerate tendon (Drengk et al., 2009; Barbon et al., 2019) and induce tissue angiogenesis in skin graft transplantation has also been proven in previous research (Wang et al., 2019; Gao et al., 2020).
Damian Jacob Sendler
MSCs placed within graphene oxide (GO) scaffolds increased osteogenic development, as shown by Nair and colleagues. This means that they might be employed in orthopedic bone repair (Nair et al., 2015). Mesenchymal stem cells were tested in a similar way using GO scaffolds, and the results showed that they could stimulate neuronal development (Kim et al., 2015). Dental pulp-derived MSCs in combination with PLLA and poly 3-hydroxybutyrate scaffolds might be used to treat cardiovascular disease (Castellano et al., 2014). ASC differentiation into chondrocytes was shown by Yin and colleagues using PLGA gelatin scaffolds treated with TGF-1 (Yin et al., 2015).
Damien Sendler: To treat spinal cord and peripheral nerve injuries, wound healing, myocardial infarction, cartilage regeneration, and bone tissue engineering, hydrogels made from decellularized adipose tissue (hDAT) have been extensively studied. Using DAT hydrogels, Mohiuddin and colleagues have demonstrated that ASC proliferation and multilineage differentiation may be supported. Additionally, the ASCs restructured the hydrogels' architecture, making them more suitable for adipose tissue regeneration similar to that seen in vivo (Mohiuddin O. A. et al., 2019). The use of ASCs and decellularized scaffolds in regenerative medicine holds promise.
For each application, "decellularization and sterilization" should be improved, as it will influence the quality of stem cell attachment and differentiation. Decellularization and sterilizing processes utilized in the fabrication of DAT hydrogels have been reported by Yang et al. and the issues that need to be handled before their usage in clinical trials have been discussed (Yang et al., 2020). There are a variety of decellularization techniques available, including biological (enzymatic digestion, DNase/RNase), chemical (isopropanol, Triton X, sodium chloride), and physical (freeze/thaw cycles, homogenization). 70 percent ethanol, penicillin and streptomycin, ethylene oxide, and UV radiation were among the most often used sterilizing methods (Song et al., 2018; Thomas-Porch et al., 2018; Yang et al., 2020).
Some detergents and enzymes used in decellularization induce the loss of key ECM components such as collagen, laminin, and glycosaminoglycans (GAGs) and the breakdown of protein-protein interactions. Despite this, these approaches have been proved to be efficient in decellularization. According to Yang et al., stem cell adhesion differentiation and immune response may be affected or triggered by chemical and enzymatic residues or cell debris. The development of 3D biomaterial scaffolds that may serve as effective in vitro models of disease pathophysiology and be utilized to test potential treatments while reducing the use of experimental animals is dependent on refining techniques for adipose tissue decellularization.
Systems for "Organs on a Chip," or "microphysiology."
Researchers may explore cell-cell, cell-ECM, and cell-tissue interactions in an in vivo-like dynamic microenvironment using microphysiological systems (MPS). With MPS, it is possible to create "organs on a chip" that may be used for drug screening and the evaluation of new therapies by assembling 3D organoids "made from cell-cell interactions in a scaffold-free way" (Zhang et al., 2017; Ronaldson-Bouchard and Vunjak-Novakovic, 2018; Wu et al., 2020; Marrazzo et al., 2021). It is possible to use MPS to grow stem cells on a layer-by-layer or interconnected cell culture chamber-by-microchannel basis (particular to the cell type). Aside from mechanical and pharmacological stimulation, they may also be used to mimic human tissue's biochemical and physiological processes in real-time. Depending on the experiment, the MPS microchannels may be sealed or perfused to regulate the flow of media between the chambers. Only a few published studies have used stem cells, including ASCs, to study MPS (Zhang et al., 2017; Paek et al., 2019; O'Donnell et al., 2020; Marrazzo et al., 2021).
Bone marrow-on-a-chip (BMoC) has been developed by Kefallinou and colleagues, which might be used to examine the stromal niche in disorders such as SLE (Kefallinoua et al., 2020). One of Lavrentieva's studies used hASCs and human umbilical cord vein endothelial cells (HUVECs) embedded in a methacrylated gelatin (GelMA) hydrogel to study the morphological changes and cellular interaction in a stem cell niche and how the stiffness of the gels plays a significant role in developing scaffolds used for clinical applications, as described in another article (Lavrentieva et al., 2020). Researchers have created a 3D microvascular network using human ASCs and human adipose microvascular endothelial cells (hAMECs) on a collagen and fibrin hydrogel scaffold to research vascular inflammation in a dynamic fluid system using this MPS (Paek et al., 2019). The data gathered by the MPS will be used to construct preclinical models of vascular and metabolic illnesses that may be used to test possible treatments. Research is still required into how mechanical stimuli impacts stem cell niche formation in physiological circumstances. There's been some evidence to suggest that interstitial shear stress could affect the capacity of ASCs to convert into adipose tissue (Bender et al., 2020).
Patients with Chron's disease, neurological degenerative diseases, atherothrombotic illnesses, long-term kidney disease, degenerative osteoarthritis are among those who are undergoing human pre-clinical and clinical trials to see if new treatments can be developed to treat these and other diseases. These trials are also looking at ways to improve recovery after ligament and tendon iatrogenic injury and to treat non-healing wounds in diabetic ulcers (Shukla et al., 2020). In spite of this, there are still a number of hurdles that must be cleared before these medicines can be certified by the FDA as safe and effective treatments.
The donor's age, body mass index (BMI), and health problems (underlying illness or comorbidities) may restrict the immunomodulatory powers of the key regulatory variables used in ASC regenerative medicine (Strong et al., 2013; Barwinska et al., 2018). Because of this, it is essential that ASCs be completely characterised and carefully tested for the presence of in vitro aging and inflammation markers that might compromise their ability to regenerate and impede their use in clinical applications Stiffness, pore size, stiffness, and biodegradability are all important factors to consider when designing scaffolds as a new therapeutic tool that mimics the in vivo milieu. More research is required in these areas. Using ASCs scaffolds in an MPS is limited by their proliferation, migration, and capacity to multi-differentiate in a co-culture system for a long time.
Regenerative medicine and tissue engineering might benefit from the use of ASCs. ASCs are still being studied in human trials for a variety of disorders despite the fact that their biologic features have not yet been completely defined. Preclinical and human clinical investigations have examined the immunomodulatory, anti-fibrotic, anti-apoptotic, and anti-oxidative activities of ASCs. The ASC secretome (conditioned media or exosomes) has also shown comparable efficacy in regenerative medicine. ASCs and ASC-derived products' therapeutic potential as cell therapies will be directly impacted by their growth and differentiation efficiency, which in turn will have a substantial influence on their therapeutic potential as cell treatments in increasingly complicated 3D systems.
More advanced therapies may be developed with less risk and adverse effect by mixing stem cells with scaffolds or microfluidic chip technologies, which is an emerging technique. Researchers may soon have new tools to treat many illnesses that traditional medicine couldn't successfully cure thanks to ASC-based scaffolds and "organs-on-chip" models. The more complex these 3D systems become, the more important it will be for researchers to address a variety of issues, such as the types of cells needed to build them, the standardization of the methodologies used to build them, the criteria for determining how well they mimic an intact organ, as well as the outputs needed for biological and efficacy assessments.
Dr. Damian Jacob Sendler and his media team provided the content for this article.