Abstract
Mesenchymal stromal cells (MSCs) comprise a heterogeneous population of multipotent stromal cells that have gained attention for the treatment of irradiation-induced normal tissue toxicities due to their regenerative abilities. As the vast majority of studies focused on the effects of MSCs for photon irradiation-induced toxicities, little is known about the regenerative abilities of MSCs for particle irradiation-induced tissue damage or the effects of particle irradiation on the stem cell characteristics of MSCs themselves. MSC-based therapies may help treat particle irradiation-related tissue lesions in the context of cancer radiotherapy. As the number of clinical proton therapy centers is increasing, there is a need to decidedly investigate MSC-based treatments for particle irradiation-induced sequelae. Furthermore, therapies with MSCs or MSC-derived exosomes may also become a useful tool for manned space exploration or after radiation accidents and nuclear terrorism. However, such treatments require an in-depth knowledge about the effects of particle radiation on MSCs and the effects of MSCs on particle radiation-injured tissues. Here, the existing body of evidence regarding the particle radiobiology of MSCs as well as regarding MSC-based treatments for some typical particle irradiation-induced toxicities is presented and critically discussed.
Highlights
Mesenchymal stromal cells (MSCs) were first isolated from the human bone marrow by Friedenstein and colleagues in the late 1960s [1, 2], but have since been described in various other tissue types such as adipose and glandular tissues, brain and umbilical cord [3,4,5,6] and many other organs
Most in vitro and in vivo studies have focused on the impact of photon irradiation on MSCs, and little is known about the particle radiobiology of these multipotent cells, which is a crucial step towards the usage of MSC-based therapies for particle radiation-associated tissue damage, e.g. after particle radiotherapy or during manned deep space flight [22,23,24]
Stem-cell based treatments using MSCs obtained from the bone marrow, adipose tissue or tonsils have been examined for osteoradionecrosis after photon irradiation in four in vivo studies and in two clinical case reports [40,41,42,43,44,45,46]
Summary
Mesenchymal stromal cells (MSCs) were first isolated from the human bone marrow by Friedenstein and colleagues in the late 1960s [1, 2], but have since been described in various other tissue types such as adipose and glandular tissues, brain and umbilical cord [3,4,5,6] and many other organs. Upon MSC administration, salivary flow rates were found significantly increased compared to the placebo group, and consistently, xerostomia symptoms decreased in MSC-treated but not in placebo-treated patients Based on these encouraging results, a follow-up trial (NCT03874572) aims to validate these findings for allogenic MSCs. So far, most in vitro and in vivo studies have focused on the impact of photon irradiation on MSCs, and little is known about the particle radiobiology of these multipotent cells, which is a crucial step towards the usage of MSC-based therapies for particle radiation-associated tissue damage, e.g. after particle radiotherapy or during manned deep space flight [22,23,24]
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