Small volume bone marrow aspirates with high progenitor cell concentrations maximize cell therapy dose manufacture and substantially reduce donor hemoglobin loss

Abstract

Background Bone marrow (BM) transplantation is a life-saving therapy for hematological diseases, and the BM harbors also highly useful (progenitor) cell types for novel cell therapies manufacture. Yet, the BM collection technique is not standardized. Methods Benchmarking our collection efficiency to BM collections worldwide (N = 1248), we noted a great variability of total nucleated cell (TNC) yields in BM products (HPC-M) with superior performance of our center, where we have implemented a small volume aspirate policy. Thus, we next prospectively aimed to assess the impact of BM collection technique on HPC-M quality. For each BM collection (N = 20 donors), small volume (3 mL) and large volume (10 mL) BM aspirates were sampled at 3 time points and analyzed for cell composition. Results Compared to large volume aspirates, small volume aspirates concentrated more TNCs, immune cells, platelets, hematopoietic stem/progenitor cells, mesenchymal stromal cells (MSCs), and endothelial progenitors. Inversely, the hemoglobin concentration was higher in large volume aspirates indicating more hemoglobin loss. Manufacturing and dosing scenarios showed that small volume aspirates save up to 42% BM volume and 44% hemoglobin for HPC-M donors. Moreover, MSC production efficiency can be increased by more than 150%. Conclusions We propose to consider small volume BM aspiration as standard technique for BM collection.

Therapeutic Applications of Stem Cell-Derived Exosomes

“…RBC lysis is a faster and more easily standardized technique which can isolate MSCs by using ammonium chloride to break down RBCs whilst not affecting the composition of stem cells [ 83 ]. From a patient standpoint, studies have shown that low-volume aspirates are associated with fewer complications, such as minimal hemoglobin loss [ 84 ]. Furthermore, this offers a more efficient methodology to generate more MSCs.…”