Bone marrow mesenchymal stem cells (MSC) are important members of the stem cell family, derived from the mesoderm and ectoderm in the early stages of human body development. They were initially found in the bone marrow, and now it has attracted increasing attention because of its multi-directional differentiation potential, hematopoietic support, promotion of stem cell implantation, immune regulation, and self-replication. MSC can differentiate into fat, bone, cartilage, muscle, tendon, ligament, nerve, liver, myocardium, endothelium, and other tissue cells under specific induction conditions in vivo or in vitro. After continuous subculture and cryopreservation, it can still differentiate into multiple cells. MSC differentiation potential can be used to repair tissue and organ damage caused by aging and disease. In all, MSC is taken as a powerful cell tool with broad applications like iPSC. As your professional research partner, the specialists of Creative Biolabs will assist you to develop and characterize MSC.
In 1968, the German scientist Frieden Stein and his colleagues firstly discovered MSCs in the bone marrow. Afterward, other researchers found that MSCs are widely present in various tissues throughout the body and MSC isolation and expansion can be achieved in vitro. MSCs can differentiate into cells of multiple tissue systems including nerve cells, osteoblasts, cartilage cells, muscle cells, and fat cells under specific conditions. They also play an important regulatory role in human functions such as hematopoiesis, immune inflammation, and angiogenesis.
Fig.1 Mesenchymal stem cells differentiate into multiple cells. (Almalki, 2016)
MSCs can regulate immunity. The activated MSCs can secrete a variety of soluble immune regulatory factors, including prostaglandin E2 (PGE2), interleukin-10 (IL-10), transforming growth factor-β (TGF-β), nitric oxide (NO), indoleamine 2, 3-dioxygenase (IDO). These cytokines and surface molecules promote the differentiation of dendritic cells and macrophages, and inhibit the proliferation, activation, and cytokine expression of TH1 and TH17 lymphocytes. TGF-β interacts with ICOSL-ICOS to stimulate T cells and B cells, increases the expression of IL-10, and reduces the production of IgE. IL-10 inhibits T cell proliferation and maturation, promotes T cell apoptosis, and restores tissue homeostasis.
In addition to their anti-inflammatory effects, MSCs also have the function of promoting tissue repair. On the one hand, this function depends on the differentiation ability of MSCs, and on the other hand, it is closely related to its regulatory function. By secreting paracrine growth factors (VEGFα, pro-angiogenesis protein factor-1, TGF-β1, insulin-like growth factor (IGF1)) to stimulate fibroblasts and macrophages to migrate to damaged tissues, thus promoting angiogenesis, and inhibiting cell apoptosis and fibrosis.
More importantly, MSCs are easy to separate, culture, expand, and purify. They still have the characteristics of stem cells after multiple passages and expansion.
The clinical research of MSC involves hundreds of diseases. By categorizing these diseases according to organ systems, we can find that the nervous system, cardiovascular, and orthopedic diseases are the three main research fields, accounting for more than 15%, and the total is more than half. In addition, the proportion of diabetes, liver, lung, gastrointestinal tract, skin, and graft-versus-host disease (GvHD) is about 5%. Up to now, the reports on the clinical application of MSC are as follows:
1. Bone diseases
The use of bone marrow MSC to treat pediatric patients with osteogenesis impaired was first reported in 2009. Osteogenesis imperfecta, also known as "fragile bone disease", is a hereditary collagen disease characterized by bone deformities and prone to fractures. These patients initially received bone marrow transplants from their HLA-matched siblings. In a short period, the number of fractures decreased significantly and the body skeleton grew significantly. However, in order to maintain long-term efficacy, these patients received an intravenous infusion of cultured bone marrow MSCs 18-34 months after bone marrow transplantation. The skeleton growth was very obvious.
Bone marrow MSC can also be used to treat hypophosphatemia. Hypophosphatemia is a rare bone mineralization disorder that can be fatal in the perinatal period and there is no curative treatment. Before treatment, an 8-month-old patient had fractures, scoliosis, and respiratory insufficiency; after receiving an intravenous infusion of bone marrow MSC from her sister, this patient experienced whole-body bone remineralization, fracture healing accelerated, and there was no new disease fracture.
2. Graft versus host disease (GvHD)
In 2004, the clinical research results of MSC in the treatment of GvHD were firstly reported. After the first bone marrow MSC transplantation, the symptoms almost disappeared in this patient with refractory grade IV GvHD. Recent systematic reviews and meta-analyses have shown that the overall response rate of MSC to steroid-resistant acute and refractory GvHD in children is 73%. In 2012, Prochymal, a commercial BM-MSC product, became the first stem cell product approved by the Canadian government for use in steroid-resistant acute childhood GvHD.
3. Spinal muscular atrophy
In 2015, it was reported that 3 patients with spinal muscular atrophy were treated with allogeneic bone marrow MSC for the first time. The neuromuscular disease scores of these patients showed significant improvement in muscle strength, including facial expression, spontaneous breathing, and speaking ability.
4. Bronchopulmonary dysplasia (BPD)
The exciting results of the first clinical trial of neonatal bone marrow MSC were reported in 2014. PNEUMOSTEM is a human cord blood-derived MSC product (expanded by fetal bovine serum in vitro culture to the sixth generation), which is locally injected through tracheal intubation to very premature newborns (27 weeks of gestation) aged 5 to 14 days. Compared with age-matched historical controls, the BPD in the treated infants was significantly reduced, and no treatment-related side effects were observed.
5. Cerebral palsy
Multiple clinical studies have shown that intravenous and/or intrathecal injection of allogeneic MSC can improve the muscle tone, strength, language, memory, and cognitive abilities of children with cerebral palsy. The improvement of brain nerve function appears to be dose-dependent.
6. Autism-spectrum disorders
In 2007, it was first proposed that stem cells could theoretically treat autism. In 2013 and 2018, clinical studies on the treatment of autism with MSC were reported respectively. The Child Autism Rating Scale, the Clinical Overall Impression Scale, and the Abnormal Behavior Checklist all showed the physical state and thinking ability of children with autism were improved greatly.
In all, MSC therapy is widely used in the treatment of various clinical diseases, and related research has made great progress. In terms of neurological diseases, spinal cord injury, multiple sclerosis, stroke, amyotrophic lateral sclerosis, and Alzheimer's disease are the most studied diseases. In orthopedic diseases, osteoarthritis, femoral head necrosis, and intervertebral disc degeneration are the main studied diseases. In terms of cardiovascular system disease, myocardial infarction is the most studied. In addition, there are many clinical studies on liver cirrhosis, Crohn's disease, interstitial lung disease, and systemic lupus erythematosus. In terms of reproductive system diseases, there are also clinical studies on the treatment of erectile dysfunction and premature ovarian failure with MSC. If you'd like to know more about our stem cell service, please directly send us an e-mail or contact us for your special requests. Creative Biolabs will provide you with full assistance in your MSC research.
Reference
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