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MicroC(3): an ex vivo microfluidic cis-coculture assay to test chemosensitivity and resistance of patient multiple myeloma cells.

ABSTRACT: Chemosensitivity and resistance assays (CSRAs) aim to direct therapies based upon ex vivo responses of patient tumor cells to chemotherapeutic drugs. However, successful CSRAs are yet to be developed. Here, we exposed primary CD138(+) multiple myeloma (MM) cells to bortezomib, a clinical proteasome inhibitor, in microfluidic-cis-coculture (MicroC(3)) incorporating the patient's own CD138(-) tumor-companion mononuclear cells to integrate some of the patients' own tumor microenvironment components in the CSRA design. Statistical clustering techniques segregated MicroC(3) responses into two groups which correctly identified all seventeen patients as either clinically responsive or non-responsive to bortezomib-containing therapies. In contrast, when the same patient MM samples were analyzed in the absence of the CD138(-) cells (monoculture), the tumor cell responses did not segregate into clinical response clusters. Thus, MicroC(3) identified bortezomib-therapy MM patient responses making it a viable CSRA candidate toward enabling personalized therapy.

SUBMITTER: Pak C

PROVIDER: S-EPMC4476551 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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MicroC(3): an ex vivo microfluidic cis-coculture assay to test chemosensitivity and resistance of patient multiple myeloma cells.

Pak Chorom C Callander Natalie S NS Young Edmond W K EW Titz Benjamin B Kim KyungMann K Saha Sandeep S Chng Kenny K Asimakopoulos Fotis F Beebe David J DJ Miyamoto Shigeki S

Integrative biology : quantitative biosciences from nano to macro 20150522 6

Chemosensitivity and resistance assays (CSRAs) aim to direct therapies based upon ex vivo responses of patient tumor cells to chemotherapeutic drugs. However, successful CSRAs are yet to be developed. Here, we exposed primary CD138(+) multiple myeloma (MM) cells to bortezomib, a clinical proteasome inhibitor, in microfluidic-cis-coculture (MicroC(3)) incorporating the patient's own CD138(-) tumor-companion mononuclear cells to integrate some of the patients' own tumor microenvironment components ...[more]

PMID: 25998180

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Project description:BackgroundPoor engraftment due to low cell doses restricts the usefulness of umbilical-cord-blood transplantation. We hypothesized that engraftment would be improved by transplanting cord blood that was expanded ex vivo with mesenchymal stromal cells.MethodsWe studied engraftment results in 31 adults with hematologic cancers who received transplants of 2 cord-blood units, 1 of which contained cord blood that was expanded ex vivo in cocultures with allogeneic mesenchymal stromal cells. The results in these patients were compared with those in 80 historical controls who received 2 units of unmanipulated cord blood.ResultsCoculture with mesenchymal stromal cells led to an expansion of total nucleated cells by a median factor of 12.2 and of CD34+ cells by a median factor of 30.1. With transplantation of 1 unit each of expanded and unmanipulated cord blood, patients received a median of 8.34×10(7) total nucleated cells per kilogram of body weight and 1.81×10(6) CD34+ cells per kilogram--doses higher than in our previous transplantations of 2 units of unmanipulated cord blood. In patients in whom engraftment occurred, the median time to neutrophil engraftment was 15 days in the recipients of expanded cord blood, as compared with 24 days in controls who received unmanipulated cord blood only (P<0.001); the median time to platelet engraftment was 42 days and 49 days, respectively (P=0.03). On day 26, the cumulative incidence of neutrophil engraftment was 88% with expansion versus 53% without expansion (P<0.001); on day 60, the cumulative incidence of platelet engraftment was 71% and 31%, respectively (P<0.001).ConclusionsTransplantation of cord-blood cells expanded with mesenchymal stromal cells appeared to be safe and effective. Expanded cord blood in combination with unmanipulated cord blood significantly improved engraftment, as compared with unmanipulated cord blood only. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00498316.).

Dataset Information

MicroC(3): an ex vivo microfluidic cis-coculture assay to test chemosensitivity and resistance of patient multiple myeloma cells.

Publications

MicroC(3): an ex vivo microfluidic cis-coculture assay to test chemosensitivity and resistance of patient multiple myeloma cells.

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