Human Immature Dental Pulp Stem Cells Did Not Graft into a Preexisting Human Lung Adenocarcinoma

Abstract

Mesenchymal stem cell (MSC)-based therapies have been considered an attractive approach for treating Huntington’s disease (HD). However, due to the pulmonary first-passage effect associated with intravenous infusion (the most commonly used route of MSC administration), there is a rising concern that the cells could be entrapped in the lungs and grafted (homing) into preexisting lung cancer. Herein, we report the case of a patient with HD enrolled in a cell therapy phase I clinical trial for HD treatment having a preexisting pulmonary nodule. The nodule was found at the trial screening. The patient was referred to a pulmonologist who considered the nodule non-cancer and authorized enrollment. The patient received four intravenous administrations of human immature dental pulp stem cells (hIDPSCs) at the dose of 1 × 10<sup>6</sup> cells/kg of body weight within 2 years. One month after the last dose, a computerized tomography scan showed nodule growth. A bronchoscopy biopsy showed primary lung adenocarcinoma. The neoplasm was surgically excised (lung superior right lobectomy). The patient is cured of the neoplasm. The tumor was sectioned into six fragments, which were subjected to RNA-seq. The transcriptome of each tumor section was compared with the transcriptome of infused hIDPSCs using two statistical approaches: principal component analysis and NOIseq. Both results demonstrated a linear distance between the hIDPSCs and the lung adenocarcinoma. These results suggest that the infused hIDPSCs neither home nor graft within the pulmonary nodule.

Stem Cells from Dental Pulp of Deciduous Teeth: Twenty Years of Experience

“…Using reduction dimension analysis (PCA or principal component analysis), we demonstrated no evidence of the hIDPSCs within the lung adenocarcinoma. This result suggests that transplanted manufactured hIDP-SCs neither home nor graft within the pulmonary nodule [104], reinforcing that the cell therapy with the NestaCell ® is safe even for patients with preexisting lung cancer.…”

Mesenchymal Stromal Cells Derived from Dental Tissues: Immunomodulatory Properties and Clinical Potential

“…Healing of the periapical tissue and the formation of functional pulp tissue [252] Intrabony lesions Autologous PDLSCs Surgery, implantation in the affected sites Reduction in probing depth [253] Cleft lip and palate Autologous SHED Surgery, implantation in a hydroxyapatite-collagen sponge Generation of bone tissue [254] Erectile dysfunction CMs SHED Injections into the corpora cavernosa of the penis Improvement of erections [255] Diabetes mellitus 2 Allogeneic SHED Intravenous Decreased glycosylated hemoglobin and glycosylated serum albumin levels and caused fever, fatigue, and rash [256] Huntington's disease associated with primary lung adenocarcinoma Allogeneic SHED Intravenous Cells did not graft (homing) in the pre-existing tumor [257] Irreversible pulpitis Autologous DPSCs…”

Clinical trials using dental stem cells: 2022 update

“…In this study, the international index of erectile function (IIEF-5), which is clinically used to screen for erectile function and to assess treatment efficacy, was increased after SHED-CM injection into the corpus cavernosum of erectile dysfunction patients[ 64 ]. A case report indicated that SHED intravenous administrations could decrease the scale of unified Huntington’s disease rating, which is designed to assess clinical performance and capacity in patients with Huntington’s disease[ 65 , 66 ]. Meanwhile, the patient with Huntington’s disease also suffered from preexisting pulmonary nodules, and SHED injection did not result in long-term tropism or homing for the patient’s lung adenocarcinoma[ 65 ].…”

“…A case report indicated that SHED intravenous administrations could decrease the scale of unified Huntington’s disease rating, which is designed to assess clinical performance and capacity in patients with Huntington’s disease[ 65 , 66 ]. Meanwhile, the patient with Huntington’s disease also suffered from preexisting pulmonary nodules, and SHED injection did not result in long-term tropism or homing for the patient’s lung adenocarcinoma[ 65 ]. In a case report by Wang et al [ 30 ], GMSCs were used to treat plaque psoriasis via bolus injection, and they observed fully cleared psoriatic lesions without recurrence.…”