Cytotronics™ Platform

Our Cytotronics™ platform uses Time-Varying Electromagnetic Field (TVEMF) technology to expand and enhance the therapeutic properties of stem cells, immune cells and for use in tissue engineering. The goal of our Cytotronics™ platform is to create optimized cell-based therapies with greater therapeutic potential than the un-modulated cells currently being used in regenerative medicine.

The origins of our Cytotronics™ platform dates back to experiments conducted at NASA to expand stem cells ex vivo and to create therapies that could be used to treat astronauts during long term space exploration. The results of those experiments revealed that Time-Varying Electromagnetic Fields (TVEMF) could be used to expand stem cells in the lab and resulted in the increased expression of dozens of genes related to cell growth, tumor suppression, cell adhesion and extracellular matrix production.

A Physics Approach to Biology – Ex Vivo Modulation

We have built upon over 15 years of research and development to create a novel therapeutic paradigm – the systematic enhancement of the biological and therapeutic properties of cells ex vivo. This allows for the creation of a precise, scalable and cost effective approach to maximize the safety and effectiveness of cell-based therapies.

While our competitors are using genetic modification and pharmacological modulation to alter and enhance the biological properties of cells, we are taking A Physics Approach to Biology™ in the use of bioelectronics to create ex vivo modulated cells with enhanced biological and therapeutic properties. Using our Cytotronics™ platform, we are able to create cells that express higher levels of key genes related to stem cell maintenance, cell growth, cell homing and engraftment. Cytotronic™ expansion of peripheral blood stem cells resulted in an over 80-fold expansion of CD34+ cells in as few as 6 days.

Our Cytotronic™ platform was shown to be able to maintain normal human neural progenitor (NHNP) cells in long term culture (180 days), undifferentiated with the ability to be cryogenically preserved then subsequently reintroduced into culture with stem and progenitor markers still intact. NHNP cells that were expanded using our technology were then shown to not be tumorigenic when introduced into nude (athymic) mice for 85 days. Multi-color Fluorescence In Situ Hybridization (mFISH) showed that there was no chromosomal damage to cells subjected to Time-Varying Electromagnetic Fields (TVEMF).

ex vivo modulation

Perivascular Cell Therapy Created Using Cytotronics™

Each year, an estimated 60,000 patients with leukemia and lymphoma need bone marrow transplantation. However, only 25,000 of those patients actually receive a transplant, primarily because the other 35,000 patients are unable to find a fully matched bone marrow donor.

Umbilical cord blood from newborn children is an excellent source of hematopoietic stem cells for stem cell transplants because their immune system is still immature and the stem cells have a lower probability of inducing an adverse immune response in patients. Furthermore, a perfect immunological match between donor and recipient is not necessary, unlike in bone marrow transplants.

However, in most cases a unit of umbilical cord blood contains too few stem cells to treat an adult patient and its use is confined above all to the treatment of children. Numerous patients have better matched cord blood products available (5/6 or 6/6 HLA match), however those products have low cell doses and are not suitable for use in adult patients. This is one of the reasons why less than 3 percent of cord blood collected in the United States is ever used. Low volume cord blood units present the opportunity to expand and/or enhance these unused cord blood units for the widespread use of hematopoietic stem cells in regenerative medicine.

Off-The-Shelf Therapeutic

Our Perivascular Cell Therapy is created using immunologically privileged and immune-modulating stem cells from a portion of the human umbilical cord and co-cultured with adipose-derived stem cells along with cord blood cells to create a perivascular cell mixture that can be used to treat malignant and non-malignant hematological disorders.

Endonovo’s cell therapy is an off-the-shelf therapeutic that can be stored indefinitely in a low temperature freeze without requiring cryopreservation. Our technologies are particularly suited to expand the use and effectiveness of low-volume cord blood units.

More In Vivo-Like Stem Cells

Our off-the-shelf therapeutic is created in a three-dimensional bioreactor using our proprietary Cytotronics™ platform to further expand and enhance the biological properties of the stem cells within the perivascular cell mixture. Our use of a perivascular co-culture in a three-dimensional bioreactor is meant to mimic the way that blood-forming stem cells renew and reside in the body. This simulated stem cell niche allows for the expansion of long-term self-renewing stem cells. Researchers had previously identified endothelial and perivascular cells as the cells that were functionally responsible for the maintenance of blood-forming stem cells (HSCs) in the body. Our technologies provide a method for the expansion of HSCs in an environment that resembles their native stem cell niche.

expansion of HSCs

Endonovo is using a three-dimensional bioreactor that allows for the large-scale expansion of blood-forming stem cells that enhances cell-to-cell contact between perivascular cells and HSCs, providing a culture method that more closely resembles the stem cell niche. As seen below, (A) cells grown in three-dimensions become more spherical that those grown in (B) static two-dimensional cultures. Cells grown two dimensionally in Petri dishes or t-flasks sink within their growth medium. These cells do not look or function like real human cells, which grow three-dimensionally in the body.

cells grown in 3 dimensional environment