What are stem cells?

Stem cells are the body’s raw materials – cells from which all other specialized cells are generated (cardiac cells, blood cells…). They have the potential to differentiate into multiple tissues. They also have the capacity of long-term self-renewal. No other cell type in the body has the natural ability to generate new cell types.

Stem cells sources

  • Embryonic stem cells
    Are pluripotent stem cells derived from the inner cell mass of a blastocyst, which is an early-stage embryo. They have the capacity to self-renew and differentiate into any cell type in the body. But their isolation results in destruction of the blastocyst, which can raise ethical issues, and they also have the risk of tumour formation.
  • Induced pluripotent stem cells (iPSCs)
    Have the same properties as embryonic stem cells but are generated by the reprogramming of a somatic cell by the introduction of transcription factors. iPSCs do not raise the same ethical issues as embryonic stem cells but they still have the risk of tumour formation.
  • Adult stem cells
    Based on the patients’ own cells, adult stem cells are a natural resource available in the human body with the potential to cure incurable diseases. They are considered among the safest products capable of regenerating multiple tissues.

Interest and promise

  • Stem cell therapy promotes the repair of dysfunctional or injured tissues by using stem cells.
  • Increase understanding of diseases 
  • Regenerative medicine: is the branch of medicine that develops methods to regrow, repair or replace damaged or diseased cells, organs or tissues… Stem cells can potentially be used in people to regenerate and repair tissues damaged or affected by disease. They are commonly used for bone marrow regeneration and transplantation in haematologic diseases.
  • Avoid organ transplantation through specialized cells: adult stem cells like CD34+ cells can repair heart tissue.

Literature

1 Ratajczak, M et al. (2019). Very small embryonic-like stem cells (VSELs). An update and future directions. Circulation Research, 124, 208–210

2 Krause, DS et al. (1996), CD34: structure, biology, and clinical utility. Blood 87:1–13

3 Lagasse, E et al. (2000), Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6:1229–1234. https://doi.org/10.1038/81326

4 Matsumoto, T et al. (2004), Circulating endothelial/skeletal progenitor cells for bone regeneration and healing. Bone 43:434–439.

5 Asahara, T et al. (1997), Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

6 Pasquet et al., Cytotherapy, 2009;11(8):1002-15

7 Wang, S-J et al. (2016), he Chondrogenic Potential of Progenitor Cells Derived from Peripheral Blood: A Systematic Review. Stem Cells Dev 25:1195–1207

8 Wojakowski et al. (2004), Mobilization of CD34/CXCR4+ […] Circulation, 110, 3213–3220CD34+ are safe

Characteristic and potential of CD34+ cells

– Easily found in bone marrow or peripheral blood
– Naturally mobilized after myocardial infraction
– Capacity to regenerate cardiac tissues
–  Are safe 

 

Endogenous CD34+ cells are mobilized from the bone marrow into the peripheral blood after an acute myocardial infarction (AMI). Chemokines secreted from the damaged heart tissue attract the CD34+ cells to home to the heart and promote repair. It has been shown that after AMI, the concentration of CD34+ cells is significantly correlated with improvement in heart function (left ventricular ejection fraction). The mobilized CD34+ cells promote heart regeneration by two different mechanisms. First, there is a paracrine effect, where CD34+ cells secrete growth factors (such as vascular endothelial growth factor) and exosomes containing pro-angiogenic miRNAs that promote neovascularization by the formation of new blood vessels. Second, there is tissue repair, by the proliferation and differentiation of CD34+ cells into cardiomyocytes and endothelial cells.

Activate the natural potential of body regeneration

CellProthera was created for the development, registration and marketing of innovative therapeutic solutions for the regeneration of organs damaged by disease or trauma from autologous blood peripheral stem cells. A very successful Proof of Concept trial showed structural and functional regeneration of myocardial tissue as well as reperfusion of an infarct zone after a recent Acute Myocardial Infarct (AMI). The final cell product ProtheraCytes® is made of CD34+ stem cells which have been confirmed to have potential for regeneration of various damaged tissues. ProtheraCytes® is now registered as an ATMP – Advanced Therapy Medicinal Product – within the classification of Tissue Engineered product by the European Medicines Agency.The therapeutic potential of ProtheraCytes® comes from two simultaneous mechanisms, a combination of paracrine effect and cell differentiation. The inflammatory scar in acute myocardial infarction secretes cardioactive chemokines which activate transplanted CD34+ cells. Activated CD34+ cells release soluble paracrine factors and exosomes that can enhance the proliferation of resident cardiomyocytes and support angiogenesis, thus reducing fibrosis and attenuating remodeling. A subpopulation of CD34+ cells express markers of endothelial and cardiomyocyte progenitor cells (Pasquet et al 2009) and the scar chemokines induce the commitment of CD34+ along the endothelial and cardiac pathways (Sahoo et al., 2011).