Human amniotic mesenchymal stromal cells (hAMSCs) as potential vehicles for drug delivery in cancer therapy: an in vitro study

Abstract

IntroductionIn the context of drug delivery, mesenchymal stromal cells (MSCs) from bone marrow and adipose tissue have emerged as interesting candidates due to their homing abilities and capacity to carry toxic loads, while at the same time being highly resistant to the toxic effects. Amongst the many sources of MSCs which have been identified, the human term placenta has attracted particular interest due to its unique, tissue-related characteristics, including its high cell yield and virtually absent expression of human leukocyte antigens and co-stimulatory molecules. Under basal, non-stimulatory conditions, placental MSCs also possess basic characteristics common to MSCs from other sources. These include the ability to secrete factors which promote cell growth and tissue repair, as well as immunomodulatory properties. The aim of this study was to investigate MSCs isolated from the amniotic membrane of human term placenta (hAMSCs) as candidates for drug delivery in vitro.MethodsWe primed hAMSCs from seven different donors with paclitaxel (PTX) and investigated their ability to resist the cytotoxic effects of PTX, to upload the drug, and to release it over time. We then analyzed whether the uptake and release of PTX was sufficient to inhibit proliferation of CFPAC-1, a pancreatic tumor cell line sensitive to PTX.ResultsFor the first time, our study shows that hAMSCs are highly resistant to PTX and are not only able to uptake the drug, but also release it over time. Moreover, we show that PTX is released from hAMSCs in a sufficient amount to inhibit tumor cell proliferation, whilst some of the PTX is also retained within the cells.ConclusionTaken together, for the first time our results show that placental stem cells can be used as vehicles for the delivery of cytotoxic agents.

Targeting the tumour stroma to improve cancer therapy

“…When combined with gemcitabine, nab-paclitaxel has substantial antitumour activity in patients with PDAC 286 . A novel strategy is the use of amniotic MSCs to deliver cytotoxic drugs to the tumour site 287 . MSCs from other origins can also be used; for example, a prodrug in which the active toxin Leu12ADT is released upon cleavage by prostate-specific antigen (PSA) was bound to microparticles that were coated onto bone marrow-derived MSCs and injected into mice, resulting in tumour shrinkage 288 .…”

Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

“…By using stem cells as drug delivery vehicles, different biological drugs have been delivered, including chemotherapeutic agents, prodrugs (10)(11)(12)(13), and genetic signals (14). One limitation of delivering chemotherapeutic agents is that they generally could not differentiate cancerous cells from normal cells.…”

Internalization of nanopolymeric tracers does not alter characteristics of placental cells

“…These results are promising for tracking hAMSC in different preclinical models, even during foetal development [38,39]. In addition, they are also grounds for investigating hAMSC tumour homing, considering our previous reports demonstrating the ability of hASMC to inhibit tumour cell proliferation, either directly [40] or after drug uptake and release [41].…”