Preclinical estimation of the number of hematopoietic stem cells required for in utero reconstitution using FB as a novel source of transplantable hematopoietic tissue
| . | Number of MNCs per mL (106) . | Number of FB-SRCs per mL . | Total number of FB-SRCs in 3.5 mL of whole blood collection . | Total number of FB-SRCs required for reconstitution . |
|---|---|---|---|---|
| Whole FB (collection at 12-18 wk) | 3.1 ± 0.6 | 9.93* | 9.93 FB-SRC/mL × 3.5 mL = 34.7 FB-SRC per collection | Based on avg wt of fetal recipient and placenta of 0.5 kg 0.5 kg × 2.85† = 1.425 FB-SRC |
| . | Number of MNCs per mL (106) . | Number of FB-SRCs per mL . | Total number of FB-SRCs in 3.5 mL of whole blood collection . | Total number of FB-SRCs required for reconstitution . |
|---|---|---|---|---|
| Whole FB (collection at 12-18 wk) | 3.1 ± 0.6 | 9.93* | 9.93 FB-SRC/mL × 3.5 mL = 34.7 FB-SRC per collection | Based on avg wt of fetal recipient and placenta of 0.5 kg 0.5 kg × 2.85† = 1.425 FB-SRC |
The total number of human FB repopulating cells (FB-SRCs) was estimated based on whole FB collection of 3.5 mL at 12 to 18 weeks' gestation (n = 22 independent samples). This volume was previously shown not to induce hemodynamic damage to the fetus. Based on this estimation, we suggest that an excess number of FB stem cells can be collected from the fetus in utero for autologous transplantation.
The total number of FB-SRCs was calculated by dividing the average number of FB-MNCs per milliliter of whole blood by the frequency of FB-SRCs per 106 MNCs (3.1 × 106/0.32 × 106).
Using the clinically accepted number of cells required for long-term reconstitution in the adult as 2 × 106CD34+ per kilogram of the recipient's body weight and a 10% enrichment of CD34+ cells upon mobilization among peripheral blood MNCs, it was estimated that 20 × 106MNCs/kg are required for engraftment. Because the frequency of adult M-PB SRCs is 1 in 7 × 106 MNCs, it was estimated that 2.85 SRCs/kg are required for reconstitution (20 × 106 MNCs/kg divided by 7.0 × 106 MNCs for 1 SRC) and was used to estimate the number of FB-SRCs needed for engraftment in the fetal recipient.