Cell-mediated drug delivery by gingival interdental papilla mesenchymal stromal cells (GinPa-MSCs) loaded with paclitaxel

Abstract

The procedure to obtain MSCs from interdental papilla is less invasive than that used for both bone marrow and adipose tissue, GinPa-MSCs are easy to expand and can be efficiently loaded with PTX. Taken together these qualities suggest that GinPa-MSCs may prove to be a good tool for cell-mediated drug delivery in cancer, particularly if related to stomatognathic system.

Drug Loaded Gingival Mesenchymal Stromal Cells (GinPa-MSCs) Inhibit In Vitro Proliferation of Oral Squamous Cell Carcinoma

“…This strategy is based on the protection of the drug from degradation, the promotion of drug uptake by tumour mass as well as lower toxicity in healthy cells 22 . To improve the above strategies we evaluated the use of MSCs for the drug delivery 9 , 13 and we optimized the use of gingiva- derived MSCs (GinPa-MSCs) to uptake and release important and widely used anticancer agents DXR, GCB and PTX. For this purpose we applied to the SCC154 squamous carcinoma cell line the procedure we previously standardized for pancreatic carcinoma cells (19).…”

“…Human gingival MSCs were isolated, expanded and characterized as previously described 13 . Briefly, the discarded gingival tissue from reductive gingivoplasty were collected in sterile conditions and transferred to the Cell Culture Laboratory to be processed.…”

“…The drug loading of GinPa-MSCs was performed by priming the cells according to a standardized procedure that use high drug dosage as previously described 9 , 13 . Briefly, subconfluent cultures (2 × 10 4 cells/cm 2 ) were exposed to 2 µg/ml PTX, or DXR, or GCB for 24 hours.…”

“…Among the different sources of MSCs, studies have been conducted using bone marrow MSCs that have some limitations particularly concerning the discomfort caused in the donors. For this purpose, the ability of different sources of MSCs to uptake/release drugs 9 – 13 has been evaluated. Among the different MSC sources, those from gingival could be an interesting model as they are easy to obtain with minimal invasive procedure and easy to expand with a few passages.…”

Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

“…Beside these minimal standards, further criteria for MSC identification may vary, making it difficult to strictly define MSCs. MSC populations with similar multilineage differentiation potentials in vitro can be obtained from many non-BM tissues, including the adipose tissue [4], placenta [5], umbilical cord, and peripheral blood [6], and even from gingival tissue [7]. In the last decade, MSCs held great promise for cell-based therapy in several disorders, including immune disorders and tumors, due to their ability to home to damaged tissues, to release bioactive molecules, and to have immunomodulatory actions.…”