Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery

Petrella, Francesco; Rimoldi, Isabella; Rizzo, Stefania; Spaggiari, Lorenzo

doi:10.3390/medicines4040087

Cited by 10 publications

(7 citation statements)

References 65 publications

(71 reference statements)

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“…Understanding the origin of CA‐MSCs may also have significant therapeutic implications. Given the migratory activity and cancer tropism of MSCs, several studies have proposed using MSCs as therapeutic vehicles . Our study suggests the source of MSCs in these studies is critical—BM MSCs could be effectively used in ovarian cancer but may be a poor source of MSCs for breast cancer studies.…”

Section: Discussionmentioning

confidence: 91%

Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma

et al. 2018

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Carcinoma‐associated mesenchymal stem cells (CA‐MSCs) are critical stromal progenitor cells within the tumor microenvironment (TME). We previously demonstrated that CA‐MSCs differentially express bone morphogenetic protein family members, promote tumor cell growth, increase cancer “stemness,” and chemotherapy resistance. Here, we use RNA sequencing of normal omental MSCs and ovarian CA‐MSCs to demonstrate global changes in CA‐MSC gene expression. Using these expression profiles, we create a unique predictive algorithm to classify CA‐MSCs. Our classifier accurately distinguishes normal omental, ovary, and bone marrow MSCs from ovarian cancer CA‐MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA‐MSCs and distinguishes cancer associated fibroblasts from CA‐MSCs. Using this classifier, we definitively demonstrate ovarian CA‐MSCs arise from tumor mediated reprograming of local tissue MSCs. Although cancer cells alone cannot induce a CA‐MSC phenotype, the in vivo ovarian TME can reprogram omental or ovary MSCs to protumorigenic CA‐MSCs (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA‐MSC phenotype. Interestingly, although the breast cancer TME can reprogram bone marrow MSCs into CA‐MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA‐MSC conversion is tissue and cancer type dependent. Together these findings (a) provide a critical tool to define CA‐MSCs and (b) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. S tem C ells 2019;37:257–269

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Section: Discussionmentioning

confidence: 91%

Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma

et al. 2018

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“…Nevertheless, non-modified MSCs are probably the best option for anticancer drug local delivery, as they can rapidly adapt themselves to culture conditions and become home to pathological tissues when injected in vivo in addition to their own antineoplastic activity. MSCs, as well as extracellular vesicles (EVs) obtained from MSCs (MSCs-EV), can release active soluble factors and play an effective immunomodulatory role [78][79][80][81].…”

Section: Drug Loading and Drug Delivery By Mesenchymal Stromal Cells (Mscs) And Their Extracellular Vesiclesmentioning

confidence: 99%

Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach

Lisini

Lettieri

Nava

et al. 2021

IJMS

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Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.

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“…MSCs have also been tested as deliverers of anti-angiogenic agents, pro-apoptotic proteins (TRAIL, for example) [221], and growth factor antagonists. Moreover, after exposure to high doses of chemotherapeutic drugs such as paclitaxel or gemcitabine, MSCs have been shown to accumulate and deliver the anti-neoplastic agent without undergoing genetic modifications and to decrease tumor growth [222,223]. Their ability to preferentially migrate toward tumor sites (primary and metastatic neoplasms) in addition to their availability, non-immunogenic nature, and relative ease of manipulation in vitro renders them attractive candidates for cell-based therapies.…”

Section: Mscs and Anti-tumor Therapymentioning

confidence: 99%

Mesenchymal stromal cells in cancer: a review of their immunomodulatory functions and dual effects on tumor progression

Galland

Stamenkovic

2019

The Journal of Pathology

114

104

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Mesenchymal stem or stromal cells (MSCs) are pluripotent cells implicated in a broad range of physiological events, including organogenesis and maintenance of tissue homeostasis as well as tissue regeneration and repair. Because their current definition is somewhat loose -based primarily on their ability to differentiate into a variety of mesenchymal tissues, adhere to plastic, and express, or lack, a handful of cell surface markers -MSCs likely encompass several subpopulations, which may have diverse properties. Their diversity may explain, at least in part, the pleiotropic functions that they display in different physiological and pathological settings. In the context of tissue injury, MSCs can respectively promote and attenuate inflammation during the early and late phases of tissue repair. They may thereby act as sensors of the inflammatory response and secrete mediators that boost or temper the response as required by the stage of the reparatory and regenerative process. MSCs are also implicated in regulating tumor development, in which they are increasingly recognized to play a complex role. Thus, MSCs can both promote and constrain tumor progression by directly affecting tumor cells via secreted mediators and cell-cell interactions and by modulating the innate and adaptive immune response. This review summarizes our current understanding of MSC involvement in tumor development and highlights the mechanistic underpinnings of their implication in tumor growth and progression.No conflicts of interest were declared. MSCs: heterogeneous cells in search of better definitionPrecise definition of stromal cell populations is still lacking. Unlike hematopoietic cell subpopulations,

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Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery

Cited by 10 publications

References 65 publications

Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma

Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma

Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach

Mesenchymal stromal cells in cancer: a review of their immunomodulatory functions and dual effects on tumor progression

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