Why use stem cells?

What dormant power lies in stem cells? How to unleash this power?

Thus far, MSCs have remained unavailable for veterinary therapies. By using them as the active pharmaceutical ingredient in the medicinal products we develop, we are pushing the boundaries of treatment for companion animals.

• MSC are the body’s natural reservoir of new cells used for self-regulated replacement of damaged or deteriorating ones.
• MSC possess immunomodulatory properties and a high capacity to multiply and differentiate into specialised tissue cells, e.g. bone cells, cartilage cells etc.
• The properties of adipose tissue-derived MSCs have found application in regenerative medicine and other fields.
• The immunosuppressive effect and very low expression of class 2 major histocompatibility complex (MHC) in MSCs enable their safe application in allogeneic cell therapy with minimal risk of rejection by the recipient’s immune system.
• Pharmaceuticals based on allogeneic stem cells can be batch-produced from single-donor starting material, and the patient can be treated without the need for collecting their biological material and harvesting their own cells.

MSC

isolated from adipose tissue can modulate the inflammatory microenvironment through the inhibition of proliferation and cytotoxic activity of T-cells, as well as the suppression of growth and maturation of B-cells and natural killer (NK) cells by engaging a range of cytokines, including interleukin IL-6, IL-10 and transforming growth factor beta. In addition, by inhibiting the maturation of dendritic cells, they induce their immune tolerance. The activated dendritic cells enhance the inductive effect of MSCs on regulatory T-cells through interleukin IL-10 creating an immunosuppressive environment that fosters regeneration processes.

Immunomodulacja. Immunomodulation. MSC Interactions between MSCs and immune cells.
Source: http://journal.frontiersin.org/article/10.3389/fimmu.2013.00175/full

The immunomodulatory properties of MSCs described in the article are one of the key modes of action in mesenchymal stem cell-based treatments. Specifically, MSCs act by:

• inhibiting chronic inflammation underlying many degenerative diseases, such as degenerative joint lesions;
• stimulating natural regenerative processes within damaged tissues, which leads to restoration of physical fitness in animals afflicted by degenerative joint lesions.

Aleksandra Klimczak:

“Improved techniques of MSC isolation and in vitro culture have made it possible to use stem cells obtained from bone marrow, adipose tissue, umbilical cord or umbilical cord blood as an excellent source of cells for supportive cell therapy – useful as a means of tissue and organ regeneration. Extensive pre-clinical and clinical studies have confirmed the effectiveness of stem cells when applied in the treatment of bone injuries and skeletal muscle regeneration, among other uses. MSCs can be used therapeutically in multiple ways – for example, by utilising their immunomodulatory properties. The cells modulate immune function through the secretion of cytokines, chemokines and trophic factors that directly affect damaged tissues.”

Arkadiusz Miążek:

“Allogeneic MSCs extensively interact with specific and non-specific immune cells, significantly modifying their proinflammatory cytokine expression profiles. It has been demonstrated that MSCs interact with mature type 1 and 2 (DC1, DC2) dendritic cells, inhibiting tumour necrosis factor alpha production and stimulating interleukin 10 expression. MSCs also affect the polarisation of T-cell immune responses towards Th2 and increase the ratio of regulatory T-cells. The physiological effect of MSCs on the cytokine profiles of immune cells lies in inducing immune tolerance and suppressing inflammatory reactions.”

MSC-based treatment of early and advanced degenerative joint lesions works by activating endogenous regenerative mechanisms – MSCs migrate from synovial fluid to the damaged site, where cells initiate the regeneration process following adhesion and chemotactic recruitment of local MSCs. This is a result of cell proliferation and stimulation of chondrogenesis with autocrine and paracrine signals, including TGF-β, coming from both the administered MSCs and the microenvironment of the damaged tissue. The tissue is reconstructed via the therapeutic chondrogenic process, restoring the functionality of the damaged joint.

The pro-regenerative effect of MSCs in the affected joint.
Source: http://www.intechopen.com/books/regenerative-medicine-and-tissue-engineering/is-the-articular-cartilage-regeneration-approachable-through-mesenchymal-stem-cells-therapies