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. 2019 Sep 12;7:217. doi: 10.3389/fbioe.2019.00217

Figure 5.

Figure 5

Tissue-engineered model approaches combining scaffolds, patient-derived materials, and primary cells. (A–I) prostate cancer (PCa) PDX osteomimicry when co-cultured with a patient-derived mineralized microtissue scaffold. (A) Schematic of melt electrowriting of medical grade polycaprolactone (mPCL) into a porous tubular microfiber scaffold. (B) SEM images of mPCL scaffold after calcium phosphate treatment to induce osteogenic properties. (C) Scaffold seeding with patient-derived osteoprogenitor cells, cultured for 12 weeks under osteogenic differentiation leading to a human osteoblast-derived tissue engineered construct (hOTEC), followed by co-culture with PDX for 3 weeks. (D) Mineralization differences in hOTECs according to patients. (E) Micro-computed tomography image of bone metastasis-derived PCa PDX (BM18) in co-culture with hOTEC shows high mineralization of both hOTEC and PDX mass after 3 weeks (Mean ± SE). (F) Photographs of BM18 PDX, cultured either alone or co-cultured with hOTEC at day 0 and after 3 weeks of culture. (G) Mineralization quantification from von Kossa staining inside PDX, shows that BM18 became more mineralized than lymph node-derived PCa PDX (LuCaP35) and endometrial cancer metastasis-derived PDX (20REC), in the presence of hOTEC. (H) Von Kossa staining shows strong mineralization in PCa PDXs (BM18 and LuCaP35) but no mineralization in the control endometrial PDX (20REC). (I) NuMA staining in BM18 PDX shows a majority of human cells (>75%, red arrows = human, yellow arrows = mouse). (J–M) PCa PDX-derived cells growth in a bone mimetic environment (BME). (J) Process schematic; PCa PDX (MDA PCa 118b and 183) were extracted from mice, dissociated in single cells, and transfected with mCherry lentivirus prior to co-culture on an osteoblast-derived microtissue made from melt electrowritten mPCL porous scaffolds populated with immortalized human MSCs differentiated into osteoblasts (dhMSCs) for 30 days prior to co-culture. (K) Multiphoton microscopy of tumor cells co-cultured with dhMSC scaffolds. (L) Growth areas of tumor cells on scaffolds ± dhMSCs shows no survival without dhMSCs and increase in the presence of dhMSCs. (M) Histology of MDA PCa 118b and MDA PCa 183 in bone and BME. Yellow and black dashed lines outline the tumor areas. (A–M) reproduced with permission from Shokoohmand et al. (2019) and Paindelli et al. (2019), respectively. ****P < 0.0001.