Method for increasing the safety of tissue engineered products for clinical use
Regenerative medicine is the replacement of diseased tissues or organs with laboratory-made cellular products (tissue engineered products = TEPs). In recent years stem cells have emerged as the most important source for TEPs. However, stem cell therapies (e.g. TEPs) carry the risk of uncontrolled cell growth (teratoma formation). In order to solve this problem, the present invention uses radiation as a non-genetic and easily practicable approach of mitotic inactivation without loss of function. Upon irradiation, there are no chemical or genetic residues or traces as with other processes that are highly problematic for a cell product from a regulatory point of view.
The goal of regenerative medicine is the replacement of diseased tissues or organs with laboratory-made cellular products (tissue engineered products = TEPs). In recent years stem cells have emerged as the most important source of "replacement cells". However, uncontrolled differentiation can lead to tumors (teratomas). This is a critical safety issue in using any cellular product of pluripotent stem cells. Potential solutions to this problem include positive or negative selection of therapeutical cells (e.g. via antibiotic resistance, suicide genes, fluorescent reporter genes, surface marker-based selection). However, these procedures are costly and it is unclear whether they would be applicable from a regulatory point of view. Thus, there is a need for a reliable, easy-to-perform method for mitotic inactivation of cellular products from pluripotent stem cells.
The present invention uses radiation as a non-genetic and easily practicable approach of mitotic inactivation. Irradiation is a suitable method for mitotic inactivation in TEPs, especially muscular TEPs, without loss of function. Two alternative approaches are chosen for this:
Fig 1.: Irradiation inhibits cell cycle activity in human heart muscle tissue. Staining and measurement (flow cytometry) of cell cycle marker Ki67 in human engineered heart muscle (EHM) 14 days after irradiation. Source: DE102018202268.2Fig 2.:Irradiation does not affect the biological activity of human heart muscle tissue(EHM). Force of contraction (FoC) of EHM with increasing extracellular calcium concentration. EHM were irradiated and then cultured for further four weeks. Source: DE102018202268.2
Regenerative medicine (replacement of diseased tissues).
Proof of concept in laboratory setting.
We have filed a German priority patent application (Applicant: Georg-August-Universität Göttingen public law foundation).
Dr. Stefan Uhle