Stem Cells And Regenerative Medicine – Through regenerative medicine, the human body may one day be able to repair and restore severe tissue damage or replace entire organs. Researchers are attempting to develop treatments that can support the healing process. Thanks to their regenerative capacity, mesenchymal stem cells (MSCs) may provide a breakthrough.
Imagine millions of tiny maintenance workers inside the human body moving to damaged areas to create new bone, cartilage, muscle and cartilage. The team consists of specially skilled craftsmen who have learned the secrets of repairing almost every type of damaged tissue in the human body. Do mesenchymal stem cells (MSCs) have a unique repair master? With over 7,000 articles on MSCs published in 2018 and 788 MSC-based clinical studies completed or ongoing (Ayala-Cuellar et al., 2019), it is clear that MSCs are undergoing intense research in academia and industry. Is the center point of. As Friedenstein and his colleagues discovered in the 1970s. They have a unique ability to renew and can vary over several generations. Because they are easy to differentiate and expand, MSCs are the most commonly used cells in regenerative medicine. Furthermore, due to their immunomodulatory properties, they provide promising therapeutic options for autoimmune, inflammatory, hematological and transplant diseases (Weiss and Dhalke, 2019).
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Cytologists obtain MSCs from sources including bone matrix, umbilical cord matrix, adipose tissue, tendon, lung, and periosteum. They use autologous and allogeneic MSCs in clinical trials. Since there are only a limited number of MSCs in the native tissue, they must be expanded
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Obtaining enough cells for therapeutic purposes (Mizukami and Switch, 2018). To grow MSCs, researchers typically rely on simple monolayer cultures, which provide a simple, low-cost, and easy-to-use platform. Roller bottles or multistage cell factories can be used to enhance the expansion of MSCs. However, new data suggests that 2D systems may limit the quality of MSCs, so the use of 3D systems may improve the survival rate of MSCs, as well as their anti-inflammatory and angiogenic properties (Petrenko et al. ., 2017).
Cultivation in bioreactors produces MSCs in large quantities, which ensures adherence to good manufacturing practices and guarantees high quality standards. Bioreactors continuously monitor and control factors such as pH, temperature, oxygen, and carbon dioxide concentrations. After expansion of MSCs, they must be harvested and processed under optimal conditions to guarantee a highly viable and viable cell product. Quality control criteria may vary between laboratories as there is no consensus as to what exact parameters would be required. However, proving MSC identity requires at least three criteria: adherence plasticity, expression of specific surface antigens and absence of others, as well as triple differentiation (Dominici et al., 2006). Other quality criteria include karyotype analysis, proof of high potency and performance testing.
In preclinical and clinical trials, scientists continue to study the therapeutic potential of MSCs, demonstrating their safety and potential for various treatments. The findings show that MSCs can successfully regenerate various tissues, including bone, muscle, nerve, myocardium, liver, cornea, airway, and skin (Han et al., 2019).
When a bone defect develops after trauma, arthroplasty, or tumor resection surgery, doctors recommend autologous or allogeneic bone grafting as a treatment option. However, limited supply, risk of infection and complications during surgery limit these procedures (Garcia-Gerreta et al., 2015 and Lozano-Calderón et al., 2016). In contrast, the osteogenic potential of MSCs makes them an excellent source for bone regeneration. Several studies have compared the osteogenic potential of MSCs from different sources such as bone marrow, umbilical cord and dental pulp, without a clear conclusion as to which type is more suitable. Recent data show that human adipose-derived MSCs have better proliferative capacity than bone marrow-derived MSCs, implying that MSCs from lipoaspirates may be useful for clinical bone tissue engineering (Bureau et al., 2017 ) may present good candidates for.
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In bone joints, the cartilage is not able to heal well or quickly due to lack of blood. Current cartilage repair techniques such as bone marrow stimulation and osteochondral transplantation have shown limited success. This has prompted scientists to look for viable alternatives and try new approaches. MSCs have been used for cartilage regeneration since pre-clinical trials in the 1990s. Newer technologies use 3D scaffolds that mimic the extracellular matrix to optimize MSC proliferation and differentiation. Hydrogels enriched with MSCs and stimulatory factors such as BMP-2/-4, insulin-like growth factor-1, and TGF promote cartilage injury repair (Yang et al., 2017). Despite a large amount of clinical trials, scientists still do not agree on the optimal cell source, and more research is needed before MSCs can be routinely used for cartilage regeneration.
Due to their self-renewal properties and diverse abilities, MSCs can regenerate damaged tissues and organs in the human body.
In addition to bone and cartilage, MSCs are also considered good candidates to support the regeneration of other muscle tissues, such as ligaments, cartilage and intervertebral discs. As the population ages, more patients develop degenerative spine diseases, experience severe back pain and require surgery. MSC-based therapy may represent valid surgical options to repair intervertebral discs, maintain biomechanics, and achieve pain relief (Orozco et al., 2011).
Additional properties of MSCs make them suitable for neural tissue regeneration. They can differentiate into neuron-like cells
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And expressing neuronal markers. Rehabilitation efforts focus primarily on two areas: damage caused by acute stroke or ischemia, and damage caused by neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, ischemic stroke, and Parkinson’s disease. By releasing several cytokines and other bioactive molecules such as TGF-ß, which regulate injury and repair processes, MSCs regulate the immune response and protect neuronal structures (Van Velthoven et al., 2012). This means that MSCs can support positive outcomes after brain injury and repair of peripheral nerves. Preclinical studies have confirmed that MSCs can improve functional recovery; However, there are only a few reports of clinical applications (Pope et al., 2018).
Going a step further, clinical trials and animal models have shown that MSCs can regenerate not only cells, but entire organs such as the heart, liver, eyeball, and airways. Transplanted MSCs can stimulate cardiac stem cells and differentiate into cardiomyocyte-like cells or regenerate blood vessels after myocardial infarction (Miao et al., 2017). In patients with cirrhosis, MSCs also help improve liver function. Indeed, MSCs can differentiate into multiple liver cell types and secrete trophic and immunomodulatory factors that support hepatocyte function, reverse fibrosis, and promote angiogenesis ( Wang et al., 2017 ). For researchers, the development of this approach to treating liver failure is urgently needed, given the number of patients on the transplant waiting list compared to the relatively small number of organs available.
Other examples of MSCs used in regenerative medicine include the treatment of kidney injuries, lung diseases, and regeneration of large-scale skin wounds (Khan et al., 2019).
Although the field of MSC research is rapidly expanding, gaps in our basic knowledge about MSCs still limit our complete understanding of their biological functions. in the last comment
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, Zipp and others, urge the scientific community to “clean up this stem cell mess.” The authors say that MSCs “have acquired an almost magical quality to everyone in the media and public consciousness,” and “have become a cell type for many unproven stem cell interactions.” They point out that although MSCs can promote functional recovery in preclinical studies, most clinical studies are still in the early stages. So far, only commercial MSC products have been approved by regulatory authorities.
For clinical applications, the safety of MSC therapies must be guaranteed. Systemic infusion of MSCs appears to be relatively safe, but such infusions can also induce tumors, inflammatory responses, and fibrosis (Fitzsimmons et al., 2018). In some cases, MSCs can become malignant cells or contribute to tumor formation. Because MSCs suppress the immune system and promote the formation of new blood vessels, these properties may support tumor growth and metastasis. During repair processes, fibrotic reactions may also occur, as MSCs can differentiate into fibroblasts.
Furthermore, researchers still need to overcome the obstacles of large-scale production of MSCs. Because MSC populations are diverse, they require different platforms and procedures for different indications. Thus, there are high costs involved in the production of these mobile products, as each application requires a specific protocol to be used. The lack of consensus on quality control standards hinders the standardization of cell manufacturing bioprocesses. Although bioreactors allow the growth of cells in controlled environments, evaluating product safety and efficacy remains a challenge. MSCs cannot be kept in culture for long periods of time, as they may lose vital functions, so scientists must expand the cell population immediately. Furthermore, serum-free, chemically defined media should be used to avoid ethical issues and immune reactions associated with the use of animal sera. Since cellular products cannot undergo the same viral inactivation processes as recombinant proteins, researchers must ensure the complete absence of contamination.
MSCs are a versatile cell population that offers multiple functions and remarkable therapeutic potential. However, scientists need this before they can send a “maintenance crew” to repair the extensively damaged tissue.
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