Stem cells

Stem cells are the body’s cells from which all other specialized cells are generated (cardiac cells, blood cells…). They have both the capacity of long-term self-renewal and the potential to differentiate into multiple organic tissues.
Stem cells in regenerative medicine is a new and breakthrough branch of medicine use to regenerate and repair damaged organs or tissues, thus and address still incurable diseases.

Literature

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

2 Wojakowski et al. (2004), Mobilization of CD34/CXCR4+ […] Circulation, 110, 3213–3220
3 Asahara, T et al. (1997), Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967
4 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
5 Long-term benefit of intracardiac delivery of autologous granulocyte–colony-stimulating factor-mobilized blood CD34 + cells containing cardiac progenitors on regional heart structure and function after myocardial infarct Pasquet et al., Cytotherapy, 2009;11(8):1002-15
6 Wang, S-J et al. (2016), The Chondrogenic Potential of Progenitor Cells Derived from Peripheral Blood: A Systematic Review. Stem Cells Dev 25:1195–1207

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

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

Characteristic and potential of CD34+ stem cells

CD34+ stem cells are mainly located in the bone marrow and can be easily mobilized into the peripheral blood2.
It has been shown that within the first week after acute myocardial infarction (AMI), endogenous CD34+ cells are mobilized in increased amounts from the bone marrow into the peripheral blood. Animal studies have shown that these spontaneously mobilized CD34+ cells migrate to the damaged heart and are retained around the scar of which they are supposed to limit stiffness and post-AMI remodeling. But their number is not high enough to compensate the loss of billions of infarcted cardiomyocytes. Thus, to achieve such a goal, it is necessary to very consistently increase the number of potentially active cells.

ProtheraCytes®

CellProthera has developed a unique GMP-compliant cell expansion process as well as a proprietary automation technology for in vitro multiplication of CD34+ stem cells. The final cell product, labelled as ProtheraCytes®, has the potential for regeneration of various damaged tissues, including the cardiac one. ProtheraCytes® is registered as an ATMP – Advanced Therapy Medicinal Product – within the classification of Tissue Engineered product by the European Medicine Agency (EMA).

The underlaying cardiac-repair mechanisms of ProtheraCytes® are multifaceted, combining a cell differentiation process and a paracrine effect. The post-AMI inflammatory scar first secretes cardioactive chemokines that

      1. Chemoattract transplanted CD34+ cells to home in the ischemic zone and
      2. Induce in-situ their multiplication and differentiation, promoting cardiac tissue repair

While,

      1. Activated CD34+ cells then release soluble paracrine factors and exosomes that can both enhance the proliferation of resident cardiomyocytes to reduce fibrosis and attenuate remodelling, and support angiogenesis, i.e. the revascularization of the repaired tissue.

 

StemXpand® V2 prototype with 5 incubators capable of treating 5 patients simultaneously.

Technology

CellProthera has chosen early on to invest in the development of an automation technology to guarantee a consistent level of quality across multiple production sites, for each patient and at an affordable price. Leading a consortium of five industrial partners and a research institute, together with the support of BPI France, CellProthera has developed a technology platform comprising of an automated device StemXpand® and a single-use kit StemPack®, compliant with GMP guidelines.