First Experience of Personalized in Situ Tissue Engineering for Thoracic Surgery of the Sarcoma Patient: MSCs-Containing Minimally Manipulated Cells and an Individualized Micropore Titanium Sternum in a One-Year Follow-Up Case Report

Abstract

Individually customized grafts have become standard for reconstructing extensive chest wall defects resulting from surgical interventions for sternal malignant neoplasms. However, the outcomes of these graft implantations can be further improved by administering patient-derived cells, which have minimal oncological risks. In 2021, a 52-year-old woman with chondrosarcoma (pT2N0M0G2, stage IIB) was admitted to the Department of Thoracic Surgery. The patient presented with a large tumor in the body of the sternum, measuring 81 × 94 × 91 mm, according to the computed tomography (CT) scan. To address this, an individualized endoprosthesis was modeled and created using the original 'pincer-dock' construction based on CT-scan screens. The mononuclear cell fraction (MNCs) was obtained from the patient's peripheral blood one week before surgery using a Haemonetics cell separation device and cryopreserved until the day of the procedure. The resulting 30 mL MNC suspension contained 12 mln cells per 1 mL. We performed flow cytometry analysis using a FACS Aria III flow cytometer to confirm the presence of mesenchymal stromal cells in the MNCs. We also performed immunostaining for S-100, a common tumor marker for benign and malignant diseases, and D2-40, a marker for the lymphatic endothelium that reacts with Kaposi's sarcoma and a subset of angiosarcomas. None of the cells were positive for either marker. Approximately 3 ml of the MNC suspension was injected into each rib edge and 30 ml into the operating field immediately after resection. The titanium endoprosthesis was placed in the sternal defect, and the body of the endoprosthesis was securely covered with a laparoscopically mobilized omental flap. After a one-year follow-up, the patient showed no signs of recurrence or post-surgical complications. These outstanding functional and cosmetic results highlight the potential for the broader clinical utilization of minimally manipulated cells in personalized medicine in oncology. These results could pave the way for wider clinical application of peripheral blood-derived minimally manipulated cells in personalized medicine as an adjuvant for titanium endoprosthesis reconstruction of osteochondral defects in patients with sarcoma.

Keywords: Endoprosthesis; Minimally manipulated cells; Regenerative medicine; Sarcoma; Stem cell transplantation; Tissue engineering.

Figure 1

MNCs flow cytometry and tissue engineering in situ: (A) flow cytogram of the MNC suspension, violet-colored and encircled - population of MSCs; (B) flow cytogram of MNC suspension, green-colored and encircled - subpopulation of CD34+ heterogeneous stem cells; (C) intraoperative injection of cell suspension in the sternal resection edge; (D) individualized titanium sternum on place: securing crab clips for fixation, and the omental flap is visible as extracted and prepared for covering. All images are published in accordance with the patient’s consent

Figure 2

Thorax CT: (A) axial view soft tissue window, and (B) bone window, shows the massive tumor located in the Manubrium sternum with retrosternal expansion; (C) three-dimensional view, and (D) CT topogram, (E) axial view, and (F) sagittal view shows the tissue-engineered titanium sternum six months after surgery; All images are published in accordance with the patient’s consent