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A physiologically based kinetic model for elucidating the in vivo distribution of administered mesenchymal stem cells.

ABSTRACT: Although mesenchymal stem cells (MSCs) present a promising tool in cell therapy for the treatment of various diseases, the in vivo distribution of administered MSCs has still been poorly understood, which hampers the precise prediction and evaluation of their therapeutic efficacy. Here, we developed the first model to characterize the physiological kinetics of administered MSCs based on direct visualization of cell spatiotemporal disposition by intravital microscopy and assessment of cell quantity using flow cytometry. This physiologically based kinetic model was validated with multiple external datasets, indicating potential inter-route and inter-species predictive capability. Our results suggest that the targeting efficiency of MSCs is determined by the lung retention and interaction between MSCs and target organs, including cell arrest, depletion and release. By adapting specific parameters, this model can be easily applied to abnormal conditions or other types of circulating cells for designing treatment protocols and guiding future experiments.

SUBMITTER: Wang H

PROVIDER: S-EPMC4770280 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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A physiologically based kinetic model for elucidating the in vivo distribution of administered mesenchymal stem cells.

Wang Haolu H Liang Xiaowen X Xu Zhi Ping ZP Crawford Darrell H G DH Liu Xin X Roberts Michael S MS

Scientific reports 20160229

Although mesenchymal stem cells (MSCs) present a promising tool in cell therapy for the treatment of various diseases, the in vivo distribution of administered MSCs has still been poorly understood, which hampers the precise prediction and evaluation of their therapeutic efficacy. Here, we developed the first model to characterize the physiological kinetics of administered MSCs based on direct visualization of cell spatiotemporal disposition by intravital microscopy and assessment of cell quanti ...[more]

PMID: 26924777

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Project description:The current study was designed to study the persistence and distribution of caprine bone marrow derived mesenchymal stem cells (cBM-MSCs) when administered intra-dermally in experimentally induced cutaneous wounds in rabbits. MSC's from goat bone marrow were isolated and their differentiation potential towards adipogenic and osteogenic lineages were assayed in vitro. The isolated cells were phenotypically analysed using flow cytometry for the expression of MSC specific matrix receptors (CD73, CD105 and Stro-1) and absence of hematopoietic lineage markers. Further, these in vitro expanded MSCs were stained with PKH26 lipophilic cell membrane red fluorescent dye and prepared for transplantation into cutaneous wounds created on rabbits. Five, 2 cm linear full thickness skin incisions were created on either side of dorsal midline of New Zealand white rabbits (n = 4). Four wounds in each animal were implanted intra-dermally with PKH26 labelled cBM-MSCs suspended in 500 µl of Phosphate Buffer Saline (PBS). Fifth wound was injected with PBS alone and treated as negative control. The skin samples were collected from respective wounds on 3, 7, 10 and 14 days after the wound creation, and cryosections of 6 µM were made from it. Fluorescent microscopy of these cryosections showed that the PKH26 labelled transplanted cells and their daughter cells demonstrated a diffuse pattern of distribution initially and were later concentrated towards the wound edges and finally appeared to be engrafted with the newly developed skin tissues. The labelled cells were found retained in the wound bed throughout the period of 14 days of experimental study with a gradual decline in their intensity of red fluorescence probably due to the dye dilution as a result of multiple cell division. The retention of transplanted MSCs within the wound bed even after the complete wound healing suggests that in addition to their paracrine actions as already been reported, they may have direct involvement in various stages of intricate wound healing process which needs to be explored further.

Dataset Information

A physiologically based kinetic model for elucidating the in vivo distribution of administered mesenchymal stem cells.

Publications

A physiologically based kinetic model for elucidating the in vivo distribution of administered mesenchymal stem cells.

Similar Datasets

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