Abstract:Mesenchymal stem cells (MSCs) participate in regeneration of tissues damaged by ionizing radiation. However, radiation can damage MSCs themselves.Here we show that cellular morphology, adhesion and migration abilities were not measurably altered by photon or carbon ion irradiation. The potential for differentiation was unaffected by either form of radiation, and established MSC surface markers were found to be stably expressed irrespective of radiation treatment. MSCs were able to efficiently repair DNA double… Show more
“…While it has been reported that MSCs are highly resistant to apoptosis after exposure to various forms of DNA‐damaging agents, treatment with the alkylating agent busulfan induced apoptosis in MSCs; a comparison between bone marrow‐derived MSCs (bmMSCs) and adipose tissue‐derived MSCs (adMSCs) demonstrated significantly higher apoptosis levels in bmMSCs . The regulation of apoptosis in MSCs depends on the expression of anti‐apoptotic proteins in these cells, and the evasion of apoptosis observed in MSCs may depend on paracrine signaling within the stem cells' microenvironment rather than DNA damage repair of individual cells . This is in line with the reported in vivo resistance of MSCs to alkylating antineoplastic drugs.…”
Section: Effects Of Chemotherapeutic Anti‐cancer Agents On Mscsmentioning
Chemotherapeutic agents are part of the standard treatment algorithms for many malignancies; however, their application and dosage are limited by their toxic effects to normal tissues. Chemotherapy-induced toxicities can be long-lasting and may be incompletely reversible; therefore, causative therapies for chemotherapy-dependent side effects are needed, especially considering the increasing survival rates of treated cancer patients. Mesenchymal stem cells (MSCs) have been shown to exhibit regenerative abilities for various forms of tissue damage. Preclinical data suggest that MSCs may also help to alleviate tissue lesions caused by chemotherapeutic agents, mainly by establishing a protective microenvironment for functional cells. Due to the systemic administration of most anticancer agents, the effects of these drugs on the MSCs themselves are of crucial importance to use stem cell-based approaches for the treatment of chemotherapy-induced tissue toxicities. Here, we present a concise review of the published data regarding the influence of various classes of chemotherapeutic agents on the survival, stem cell characteristics and physiological functions of MSCs. Molecular mechanisms underlying the effects are outlined, and resulting challenges of MSC-based treatments for chemotherapy-induced tissue injuries are discussed.
“…While it has been reported that MSCs are highly resistant to apoptosis after exposure to various forms of DNA‐damaging agents, treatment with the alkylating agent busulfan induced apoptosis in MSCs; a comparison between bone marrow‐derived MSCs (bmMSCs) and adipose tissue‐derived MSCs (adMSCs) demonstrated significantly higher apoptosis levels in bmMSCs . The regulation of apoptosis in MSCs depends on the expression of anti‐apoptotic proteins in these cells, and the evasion of apoptosis observed in MSCs may depend on paracrine signaling within the stem cells' microenvironment rather than DNA damage repair of individual cells . This is in line with the reported in vivo resistance of MSCs to alkylating antineoplastic drugs.…”
Section: Effects Of Chemotherapeutic Anti‐cancer Agents On Mscsmentioning
Chemotherapeutic agents are part of the standard treatment algorithms for many malignancies; however, their application and dosage are limited by their toxic effects to normal tissues. Chemotherapy-induced toxicities can be long-lasting and may be incompletely reversible; therefore, causative therapies for chemotherapy-dependent side effects are needed, especially considering the increasing survival rates of treated cancer patients. Mesenchymal stem cells (MSCs) have been shown to exhibit regenerative abilities for various forms of tissue damage. Preclinical data suggest that MSCs may also help to alleviate tissue lesions caused by chemotherapeutic agents, mainly by establishing a protective microenvironment for functional cells. Due to the systemic administration of most anticancer agents, the effects of these drugs on the MSCs themselves are of crucial importance to use stem cell-based approaches for the treatment of chemotherapy-induced tissue toxicities. Here, we present a concise review of the published data regarding the influence of various classes of chemotherapeutic agents on the survival, stem cell characteristics and physiological functions of MSCs. Molecular mechanisms underlying the effects are outlined, and resulting challenges of MSC-based treatments for chemotherapy-induced tissue injuries are discussed.
“…Therefore, additional functional features are used to characterize MSCs, among them the cells' fibroblast-like spindle shape, the ability to adhere to plastic surfaces and their differentiation potential along the ostogenic, adipogenic and chondrogenic lineages [2,7]. Several publications have demonstrated a relative radioresistance for MSCs (reviewed in [8]); and the defining stem cell properties have been shown to remain unaffected even by high doses of ionizing radiation [9][10][11][12][13][14][15].…”
“…5,6 Thus, knowledge regarding the effect of IR on tissue-resident MSC is crucial and well-investigated for bmMSC, adipose tissue MSC (adMSC) and umbilical cord MSC (ucMSC). [29][30][31][32][33][34][35][36][37][38][39][40] As a therapeutic approach, study groups applied MSC for tissue regeneration in patients with diabetic ulcer and necrotic osteolysis. 41,42 In contrast, little is known about IR-sensitivity of MSC derived from mucosa of the head and neck region or the parotid gland.…”
Background
Tissue‐resident mesenchymal stem cells (MSCs) possess the ability to migrate to areas of inflammation and promote the regeneration of damaged tissue. However, it remains unclear how radiation influences this capacity of MSC in the head and neck region.
Methods
Two types of MSCs of the head and neck region (mucosa [mMSC] and parotid gland [pMSC]) were isolated, cultured and exposed to single radiation dosages of 2 Gy/day up to 10 days. Effects on morphology, colony forming ability, apoptosis, chemokine receptor expression, cytokine secretion, and cell migration were analyzed.
Results
Although MSC preserved MSC‐specific regenerative abilities and immunomodulatory properties following irradiation in our in vitro model, we found a deleterious impact on colony forming ability, especially in pMSC.
Conclusions
MSC exhibited robustness and activation upon radiation for the support of tissue regeneration, but lost their potential to replicate, thus possibly leading to depletion of the local MSC‐pool after irradiation
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