How Can I Invest In The Regenerative Medicine And Tissue Engineering Sector? – Differential effects of extracellular vesicles from different human stem cells on the behavior of isogenic cortical spheroids.
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How Can I Invest In The Regenerative Medicine And Tissue Engineering Sector?
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Stem Cell & Regenerative Medicine Predictions
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By Yu Han Yu Han Scilit Preprints.org Google Scholar 1, 2, †, Xuezhou Li Xuezhou Li Scilit Preprints.org Google Scholar 1, 2, †, Yanbo Zhang Yanbo Zhang Scilit Preprints.org Google Scholar 3, *, Yuping Han Yuping Han Scilit Preprints.org Google Scholar 4, *, Fei Chang Fei Chang Scilit Preprints.org Google Scholar 1, * and Jianxun Ding Jianxun Ding Scilit Preprints.org Google Scholar 2
The Need For Adherent Cell Manufacturing: Production Platform And Media Strategies Drive Cell Production Economics
Key Laboratory of Ecomaterial Polymers, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, China
Received: July 12, 2019 / Reviewed: August 5, 2019 / Accepted: August 6, 2019 / Published: August 13, 2019
In recent decades, the biomedical applications of mesenchymal cells (MSCs) have attracted increasing attention. MSCs are easily extracted from bone marrow, fat and synovium and differentiate into different cell types according to the requirements of specific clinical applications. Because MSCs do not present important complement structures and do not stimulate immune cells, they are not detected by immune surveillance and do not lead to rejection after transplantation. These properties make them biomedical candidates, especially for tissue work. We present a brief overview of MSC production methods and their post-differentiation potential, an overview of early preclinical and clinical applications in regenerative medicine, and discuss future challenges.
Since the discovery of spindle-shaped cells attached to bone marrow in plastic cells in the mid-1970s, science has come a long way, and studies have shown that these cells can differentiate into osteoblasts and chondrocytes [2, 3]. Mesenchymal cell (MSC) production, culture, and production techniques have improved, and almost all types of MSCs derived from various tissues are now able to differentiate into osteocytes and the final generation [ 4 ]. Rapid advances in molecular biology and MSC transplantation techniques have benefited applications in regenerative medicine.
Reconstructive And Regenerative Medicine
MSCs are the best source of cells for tissue regeneration due to their good sequencing properties. MSCs are present in almost all tissues, including bone marrow, adipose tissue, and synovium, and are readily shed. MSCs can differentiate into almost all cell lineages, so their progeny can differentiate into specific regions (Figure 1). Their immunological properties, including anti-inflammatory, immunoregulatory and immunosuppressive properties, contribute to their potential role in immune tolerance agents [7,8].
Many studies have investigated MSCs for cell regeneration in several animals in vitro; The tests are not limited to correct authentication. Several clinical reports confirm the potential effectiveness of MSC-based cell therapy; although its effectiveness is limited, the results are encouraging. We present a brief overview of MSC production methods and possible subsequent differentiation opportunities, as well as an overview of the future applications of different MSCs in regenerative medicine and the challenges.
The abundant source of MSCs is an important basis for their extensive research and applications. It is known that MSCs can be isolated from various tissues such as bone marrow, adipose tissue, and synovium, and human blood, bone marrow, and bone marrow are the main sources of MSCs.
MSCs in different tissues and organs except bone marrow with different cells from human umbilical cord blood were first reported in the early 2000s [9]. Adipose tissue was subsequently introduced as the most abundant source of MSCs in 2001 [ 10 ], and synovial MSCs (SMSCs) were successfully isolated. MSCs have been identified from other tissues or organs, and protocols have been developed for their generation, identification and culture (Figure 2 and Table 1) [12, 13, 14, 15, 16, 17, 18, 19, 20, 21; 22, 23, 24, 25, 26, 27, 28, 29, 30]. Figure 2 and Table 1 describe the general protocol used for MSC extraction. Briefly, the process involves isolation of differentiated cells, lysis to obtain cells, and culture for 3 to 5 days, followed by rejection of unsuitable cells and continuous culture of cells near the desired threshold. The primary culture medium for MSCs contains Dulbecco’s modified low glucose medium (LG-DMEM) with 1% (w/v) antibiotic/antimycotic and 10% (v/v) bovine serum (FBS). In addition, Table 1 lists the various properties expressed on the MSC surface. In particular, the rabbit is the most used animal species in experiments involving cartilage or bone tissue regeneration, and MSC identification should be more focused. In addition, the cell surface labeling of rabbit MSCs requires further confirmation.
Next Generation Stem Cells — Ushering In A New Era Of Cell Based Therapies
Multidirectional differentiation ability is one of the most important properties of MSCs. In addition, different cell sources affect MSCs’ tendency to differentiate and proliferate.
There is a growing number of publications dealing with the differentiation of MSCs [47]. The transcriptome, proteome, immunophenotypic, and immunological functions of different types of MSCs are different, indicating that MSCs have a unique potential difference. Because MSC is a unique property, the variation force affects the amount of MSC; MSCs of different cellular origins show different propensities to differentiate into different cell lineages, such as osteoblasts and chondrocytes. As an important source of MSCs for tissue engineering, bone marrow MSCs (BMSCs) show high potential for osteogenesis and chondrogenesis under the regulation of differentiation [48], and SMSCs show increased and chondrogenic potential compared to adipose-derived MSCs. (ADSCs) [49] umbilical cord blood-derived MSCs (UCB-MSCs) show biological advantages over other mature sources, such as their ability to be cultured for long periods, extensive expansion, significant delay in consciousness, and high anti-inflammatory effects. L]. Researchers should choose the desired MSC format according to the specific objective. Table 2 summarizes the primary and live trials and the different conditions based on previous studies.
So far, MSCs have been widely studied and applied in regenerative medicine. In this section, we summarize the most recent reports of preclinical and clinical studies with different types of MSCs in tissue engineering. Topics generally focus on soft tissue reconstruction, including those related to the musculoskeletal system, nervous system, myocardium, liver, bone, arteries, and skin, as shown in Figure 3.
Bone loss is often associated with recovery from trauma, revision arthroplasty, or tumor resection surgery. Autologous bone transplantation represents the gold standard treatment strategy, although it has many disadvantages, including limited bone marrow, (2) increased operative time and blood loss, (3) disruption of bone structure at the donor site, and (4) donor site infection. [51] . An allograft carries the risk of disease and/or infection [52]. Therefore, MSC-based bone regeneration is considered the best method [53].
Immunological Barriers To Haematopoietic Stem Cell Gene Therapy
The differentiation potential of MSCs into osteoblasts has been recognized [ 2 , 3 ], and BMSCs are the most commonly used osteoblastic differentiation cells [ 2 ]. Comparative studies evaluating the osteogenic potential of other types of MSCs have not produced definitive conclusions. On the other hand, UCB-MSCs have better angiogenic capacity, supporting greater blood flow in bone regeneration [ 54 ], which promotes rapid tissue regeneration. In addition to BMSCs, human dental stem cells (hDPSCs) have excellent vascular differentiation potential by differentiating into osteoblasts, which in turn supports bone regeneration [55]. However, these HDPs were studied in the vessels of the vascularized dental pulp; therefore, this is a limited source for further research and application. Because ADSCs can be isolated from liposuction with high purity and minimal donor site morbidity or patient discomfort, ADSCs are considered to have the greatest potential as a primary source of bone tissue [ 48 , 56 , 57 ]. Further comparative studies and research are needed to identify other tissue sources with applications in bone regeneration.
Stimulatory factors play an important role in directing MSC differentiation into target cells in vitro. The most common factor involved in osteogenesis is bone morphogenetic protein-2 (BMP-2), which is normally inactive for the development of osteoblastic differentiation. BMP-2 has a strong osteogenic potential, which can be assessed by osteoblast activity and/or expression of bone markers such as alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) [ 58 , 59 , 60 ]. BMP-VII growth factor-β (TGF-β)/SMAD signaling CD105.
MSCs promote expression