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.
Highlights
In 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
We show that PTX is released from human amniotic mesenchymal stromal cells (hAMSC) in a sufficient amount to inhibit tumor cell proliferation, whilst some of the PTX is retained within the cells
Conclusions we demonstrate that mesenchymal stromal cells from the amniotic membrane of human term placenta are highly resistant to the cytotoxicity of PTX
Summary
In 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. Non-stimulatory conditions, placental MSCs 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. This occurred through cell cycle arrest in the G0/ G1 phase, and affected hematopoietic [lymphoid (KG1a, Jurkat), myeloid (KG1, U937)], and non-hematopoietic (Girardi heart, Hela, Saos) tumor cells Owing to this property and to the ability of amnion-derived stem cells to target tumor sites [22], we investigated if hAMSCs were able to uptake the chemotherapeutic agent paclitaxel, and be considered as a means of drug delivery for anti-tumor therapy
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