Mesenchymal Stem Cells (MSCs) Role in Regenerative Medicine

 

Over the past ten years or so, there has been an increasing use of stem cells in the treatment of various health-related issues or disorders. Stem cell therapy for blood disorders has been successfully used for non-blood disorders.

Extensive research by many health research institutes around the world has shown that mesenchymal stem cells (MSCs) provide a promising solution for the treatment and regrowth of human tissues. It is due to their ability to differentiate into multiple cell types, self-renew, proliferate outside the body for extended periods, have paracrine properties, and regulate the immune system.

MSCs are advantageous in that they can nurture the growth and diversification of other stem cells, in addition to discharging bioactive molecules essential to tissue repair. Owing to these beneficial qualities, MSCs are regarded as having a considerable therapeutic function in the medical practices. As such, we herein reviewed the most current trials conducted to assess the efficiency of MSCs in conditions including neural, liver, kidney, bone, heart diseases, and wound healing.

Stem Cells Role in Regenerative Medicine

Over the past few years or so, several studies by clinical research organizations have indicated that cellular therapy has made significant advances in laboratory and animal research. Stem cells possess the ability to reproduce themselves and transform into various types of cells, thus playing a role in the natural healing process. Adult and pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have been identified as potential sources for tissue regeneration.

Pluripotent stem cells (PSCs) possess a significant capacity for both pluripotency and self-renewal, thus rendering them a crucial therapeutic alternative for addressing diseases. Nevertheless, the utilization of these cells presents ethical concerns as it necessitates the separation of embryonic stem cells (ESCs) from blastocyst-stage embryos, leading to the destruction of embryos.

Studies by clinical research organizations have shown that iPSCs can regenerate in a pre-clinical setting, and the first clinical trial for treating age-related macular degeneration has been conducted. However, the risk of tumours forming remains unresolved. Due to these limitations, researchers have turned to investigating adult stem cells, which are multipotent stem cells found in the tissues and organs of adults. Numerous studies have reported that stem cell therapy can regenerate and repair injured organs in vivo, such as bone repair, wound healing, dental tissue inflammation, and ischemic cardiac tissue, by differentiating stem cells and producing specific new cells.

Furthermore, several research investigations have showcased that adult stem cells nurtured in a controlled environment can release different molecular factors that possess regenerative properties. These factors include attributes like anti-apoptotic, immunoregulatory, angiogenic, and chemoattractant effects. Hematopoietic stem cells (HSCs) and MSCs, both adult stem cells, are frequently utilized since they can be obtained from individuals afflicted with various diseases.

Mesenchymal Stem Cell

Mesenchymal stem cells (MSCs) found in the bone marrow possess the ability to renew themselves and differentiate into multiple cell lineages. They can be obtained from various tissues and organs, such as adipose tissue, Wharton's jelly, peripheral blood, umbilical cord, placenta, amniotic fluid, and dental pulp. Over the past few decades, MSCs have demonstrated a range of biological functions, including differentiation into different cell types, modulation of the immune response, promotion of blood vessel formation, prevention of cell death and fibrosis, attraction of other cells, and facilitation of tissue repair.

Mesenchymal stem cells (MSCs) possess several attributes that render them appropriate for therapeutic cellular treatments. They display stem cell properties, can be readily procured from diverse origins, can be swiftly expanded for clinical utilization, entail fewer ethical considerations than embryonic stem cells, present a reduced likelihood of teratoma development compared to induced pluripotent stem cells and can migrate to damaged tissue via chemical attraction, thus providing advantageous prospects for diverse therapeutic applications.

Furthermore, MSCs can release various bioactive substances, including proteins, growth factors, chemokines, microRNAs, and cytokines, indicating their potential for diverse applications.

Bone Marrow Mesenchymal Stem Cell-Based Regenerative Medicine

Latest data have revealed the effects of Mesenchymal Stem Cell in the regeneration or treatment of various disorders such as

Neural regeneration

The utilization of BMSCs has displayed immense potential in   neurological disorders treatment, instilling a glimmer of hope in patients grappling with such conditions. Amongst these conditions is amyotrophic lateral sclerosis (ALS), otherwise known as motor neuron disease, characterized by the gradual deterioration of motor neurons, culminating in paralysis and muscle frailty.

Numerous clinical trials have showcased considerable alleviation of symptoms thus related to spinal cord injuries (SCI) through MSC therapy. Furthermore, the implementation of ASI, Spinal Cord Independence Measure (SCIM-III), and International Standards for Neurological and Functional Classification of Spinal Cord (ISCSCI-92), has unveiled remarkable enhancements in functionality after MSC injection. It is crucial to note that no severe adverse effects have been linked to the administration of MSCs.

Liver regeneration

The capacity of BMSCs to transform into endodermal lineages, particularly cells resembling hepatocytes, presents an appealing option for addressing liver ailments. Several clinical investigations have showcased the practicality and effectiveness of BMSC therapy among liver disease patients. These studies have revealed that MSCs have a noteworthy impact in reducing ALP and GGT levels. However, there were no substantial alterations observed in serum AST, ALT, total bilirubin, albumin, prothrombin time activity, or immunoglobulin M levels.

Research reports from health research institutes have revealed that the application of MSCT drastically improved laboratory values such as serum total bilirubin and MELD scores compared to the control group. Also, the mortality rate from multi-organ failure and occurrence of grave infections was found to be lower in the intervention group than in the control. It illustrated the safety and efficacy of peripheral administration of allogeneic BMSCs to people suffering from HBV-associated ACLF, thus leading to improved survival rates through augmented liver functioning and minimization of severe infections. All things considered, MSCT was perceived to beneficially improve the clinical state of these patients, reduce liver fibrosis, and prevent the disease from progressing.

Kidney Regeneration

Renal cells can be detrimentally affected by many types of ischemic and toxic trauma, inciting inflammation and cell death that can bring about kidney harm. Inflammation has a significant influence on the injury of renal cells as well as in the wake of cellular rejuvenation. Multiple research has revealed that MSCs can be helpful in acute and chronic renal injuries.

Heart Regeneration

Heart disease is the number one and most common diagnosis and the primary source of mortality. When cardiomyocytes experience damage due to ischemia and other causes, the remaining healthy cells cannot expand in number, and any deceased cells are replaceable with non-contractile, fibrous tissue, which leads to impaired functioning and intensifies the advance of heart failure. In the face of the growing population of people with heart issues, a revolutionary solution to restoring ailing hearts is necessary. Regenerative medicine and cell therapy represent potential therapies for treating heart ailments. According to research, implanting BM-derived and cardiac stem cells into struggling hearts seems to have a positive impact on function.

Clinical trials at a clinical research organization showed that after administering allogeneic BMSCs to patients with chronic stroke, there was an improvement in their Barthel Index scores. Further, electrocardiograms, laboratory tests, and CT scans of the chest/abdomen/pelvis all pointed towards the conclusion that BMSCs could improve the clinical symptoms in stroke patients. Overall, BMSC therapy is a successful, achievable, and secure method that greatly enhances cardiac functioning and patients' quality of life.

Bone Regeneration

In clinical studies, bone regeneration is a highly researched topic as it is integral to treating conditions like fractures, osteoarthritis, and osteoporosis. Traditionally, autologous bone grafts were used to introduce osteoinductive, bone-conducting, and histo-compatible elements to the site of bone diseases. However, this method often entails pain, extended recovery time, and unpredictable absorption. Recently, a significant advancement in tissue regeneration techniques has made mesenchymal stem cells appealing for bone formation.

A pilot study was conducted to assess the efficacy of allogeneic BMSCs in bone fracture treatment. Each participant was administered with percutaneous implantation of autologous BMSCs, ranging from 5 to 10 × 107 cells, into the fracture site. Following the intervention, there was a significant improvement in the Tomographic Union Score (TUS) and Global Disease Evaluation (GDE) scores and a decrease in palpation pain. To further validate these results, several other studies examined the effect of BMSCs in patients with osteoarthritis (OA). One clinical phase I/IIa trial involved participants with late-stage Kellgren–Lawrence knee OA injected with varying doses of BMSCs, ranging from 1 × 106 to 50 × 106. These patients demonstrated improved Knee Injury and Osteoarthritis Outcome Scores (KOOS) in pain, symptoms, and quality of life.

Collectively, the findings suggest that BMSCs can be a viable, safe, and effective option for bone regeneration, considerably enhance the clinical outcomes of patients, and halt the progression of disease.

Wound Regeneration

The skin is composed of several layers with different functions, which support internal organs and serve multiple biological purposes. Generally, its healing process is composed of four stages: hemostasis, inflammation, proliferation, and maturation. Mesenchymal Stem Cells (MSCs) can play a role in every step, thus helping to reduce scarring and promote regeneration. To do this, MSCs migrate to the injury site, inhibit inflammation, and foster the growth and differentiation of fibroblasts, epidermal cells, and endothelial cells.

MSCs have been proven successful in multiple pre-clinical trials, thus prompting further examination in the clinical studies. Results demonstrate that BMSCs administered autologously can be implemented effectively without any kind of undesirable consequences. Furthermore, experiments concerning adipose-derived stem cells found them advantageous for full-thickness dorsal skin wounds in diabetic mice, producing reduced ulcer sizes or full wound closure.

Way Forward

Over the last few decades, advances in isolation, culture, and differentiation techniques have enabled MSCs to become increasingly relevant for clinical treatments for disorders and tissue regeneration. MSCs possess several beneficial properties that make them the go-to option for regenerative medicine, such as their immunomodulatory power to heal immune system abnormalities, their ability to release growth factors, and the potential to become many types of cells.

Multiple clinical trials have determined that autologous and allogeneic MSCs are suitable resources for tissue formation. Autologous MSCs are generally preferred for safe administration due to their reduced immunological risk, despite the absence of reported issues from allogeneic MSC-based therapies. Based on the evidence gathered, it is clear that MSC administration is much more successful, and the effectiveness of MSC therapy for bone and heart conditions has been solidly established.

How do Research and education Centre's like the International Institute of Innovation & Technology Kolkata play a crucial role?

At I3T, a pioneering health research institute in Kolkata, researchers focus on exploring MSC biology from Wharton Jelly of the umbilical cord. In pre-clinical and clinical studies, it has been discovered that these stem cells hold an immunomodulatory function, most likely stemming from their embryonic origin, which renders them immune-privileged. Alongside the stem cells, the conditioned media and extracellular vesicles secreted by MSCs also contain a high potential for therapeutic interventions. It is critical to understand the role of MSCs in conditions of musculoskeletal disorders such as fractures, osteoarthritis, muscle, and fat-related diseases, as it is the key to unlocking the regenerative capacity of these stem cells and helping patients suffering from such ailments.