PMC9149538_01
Time-line of hIDPSC administration in an HD patient with a silent pulmonary nodule following phase 1 clinical protocol and pulmonary lung nodule evolution between December 2017 and December 2020.
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F1
The patient received 3 monthly IV administrations of hIDPSCs (which correspond to the investigational product NestaCell ), using the cell dose of 106 cells/Kg weight (Fig. 1): April 3, 2018, May 8, 2018, June 5, 2018.
PMC9149538_02
CT and PET/CT showing the pulmonary nodule growth (verified in August 2020, after 2 years of the third hIDPSC IV infusion). PET/CT shows hypermetabolism compatible with granulomatous or neoplastic disease. PET/CT, positron electron tomography.
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F2
August 10, 2020. A new CTscan made per protocol in August 31, 2020, showed nodule enlargement (14 x 23 x 24 mm, Fig. 2). It showed nodule hypermetabolism, compatible with granulomatous or neoplastic disease (Fig. 2).
PCA results showing the linear distance of the main component of hIDPSCs in relation to the main enrolled in the clinical trial. Greater distance from fragment 1 (collected from an area adjacent to the neoplasm margin), as well as the greater distance from fragment 4 (tumor core) in relation to fragments 2/3 and 5/6 (distally located in relation to the tumor core). This result reflects intra-tumoral heterogeneity.
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F3
In addition, the results of PCA showed a linear distance between the adenocarcinoma (samples 2-6) and lung tissue fragments adjacent to the lung cancer (sample 1, Fig. 3). Results also showed that sample 4, obtained from the tumor core, was linearly distant from samples 2/3 and 5/6, all near the tumor edge (Fig. 3). However, the PCA results also showed a significant linear distance between the adenocarcinoma (samples 2-6), the healthy lung tissue (sample 1), and the hIDPSCs (sample 7, Fig. 3), suggesting the absence of hIDPSCs within the tumor tissue.
Differential expression analysis (nonparametric) by NOIseq showing that genes overexpressed in hIDPSCs are not expressed in lung adenocarcinoma fragments. Red dots indicate differentially expressed genes, and black dots, genes commonly expressed across samples.
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F4
Most transcripts of the hIDPSCs are not found in the adenocarcinoma transcriptome (Fig. 4).
CT and PET/CT performed in July 2021 as part of the follow-up of the patient showing no cancer recurrence or metastasis after the surgical treatment. PET/CT, positron electron tomography.
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F5
The surgery was considered curative for the neoplasms stage (Fig. 5).