From mesenchymal stem cells (MSCs) to cell therapy: safe and mature technologies
Cell therapy, an important field of regenerative medicine, is changing the current practice of medicine by addressing the root causes of disease rather than symptoms, by seeking to repair, replace, or regenerate organs, tissues, or cells, or to modulate the metabolic processes in the human body.
MSCs can be isolated and cultured from a variety of adult tissues, mainly bone marrow, adipose tissue, umbilical cord, and placenta. MSCs are said to be pluripotent because they can differentiate into different cell types. They also secrete various molecules (paracrine effect), and play a key role in cellto-cell communication.
Overall safety of MScs has been demonstrated in over 800 clinical trials.
Several cell therapy products using MSCs have been approved in the European UnIon, the US and Asia.
Umbilical Cord MSCs for allogeneic therapy
Cell therapy is said to be autologous when stem cells are collected on the patient himself. The therapeutic cells will be perfectly tolerated by the patient’s immune system. However, this solution has a number of weak points: preparation of cells and treatment takes more time than the ready-to-use stem cells, cells must be produced in the same hospital where the patient is treated, with high manufacturing costs, its regulatory approval is complex and autologous therapies are therefore more complicated to industrialize and commercialize.
When the therapeutic stem cells are taken from a person other than the patient, the cell therapy is called allogeneic. The use of allogeneic cells may cause immune tolerance problems, donor cells beingrecognized by the patient’s immune system as foreign elements and eliminated. Mesenchymal stem cells, on the other hand, underexpress HLA markers and secrete immunosuppressive factors that limit immune responses. No immunosuppressive therapy is therefore necessary when using allogeneic MSCs. They can be produced in GMP manufacturing facilities, distributed off-the-shelf, such as a conventional medicines. COGS is reduced, industrialization and marketing are easier.
Placental MSCs are the most interesting cells for developing allogeneic cell therapies : the original tissues, cord or placenta, are abundant and easy to collect, in a on-invasive way, after birth . Cord MSCs also have a higher proliferative potential greater than bone marrow MSCs and are hypoimmunogenic, that is, well tolerated by the recipient patient’s immune system.
Umbilical Cord MSCs: the easiest way to allogeneic cell therapy
|CSM Characteristics||Clinical and industrial applications||Bone Marrow/ Adipose Tissue||Umbilical Cord|
|Plasticity of differentiation into several cell lineages.||Wide range of potential therapies||✓✓✓||✓✓✓|
|Secretion of factors that stimulate tissue repair, anti-inflammatory, anti-fibrotic effects||Wide range of potential therapies||✓✓✓||✓✓✓|
|Proliferative potential||Reduced costs of manufacturing||✓||✓✓✓ 3X higher|
|Endothelial differentiation potential|
(Chen MY & al, Exp Hematol. 2009)
|Neovascularization of tissues/Applications to ischemia-reperfusion and cicatrisation||✓||✓✓✓|
|Low immunogenicity with significant immunosuppressive ability||Allogeneic therapy (donor different from recipient)||✓||✓✓✓|
|Sampling, storage and transport||Advantage in the manufacturing process||✓||✓✓✓ Abundant sources, easy to collect post-partum|