Does the starting blood fraction move reprogramming efficiency more than the delivery class?

Answer

The corpus does not show that the starting blood fraction moves reported efficiency more than the delivery class does, and it does not show the reverse. No verified paper ranks both effects in a matched percentage design. The fraction effect is real in some papers and absent in others, even within the same delivery class: Okumura 2019 gives 0.17% for bulk PBMC against 5.58% for CD34+-enriched cells with one Sendai vector, in one donor b8583100, whereas Ye 2013 gives 0.05%-0.06% for CD34+ against 0.02%-0.27% for bulk MNC with Sendai, a range that overlaps 9b19c845. The nearest within-paper candidate against the retired hypothesis is Merling 2013: one blood sample, CD34+-enriched, gave 7 colonies from 14 mL with a lentivirus and more than 120 colonies from 6 mL with Sendai, but at different doses and counted per mL of blood, not per input cell, so it is suggestive and not a refutation f925d777. This is a statement about this corpus, not a claim that no such paper exists.

Summary

• The fraction effect is not a fixed multiplier. Within one delivery class it ranges from none to tens-fold. Mack 2011 reports, in a verbatim quotation from the paper, that efficiency was "approximately 2 to 8 fold higher when beginning with cells purified for CD34 expression in 9 out of the 10 donors compared to those from PBMCs (p = 0.007)" with episomal plasmids e3bddedb. Liu 2015 gives up to 0.033% for MNC against 0.148% for cord-blood or fetal-liver CD34+ cells, about 4.5-fold ce0f63cb. Okumura gives about 33-fold b8583100. Lam 2022 gives 0.02%, 0.02% and 0.02% for PBMC, CD3+ and CD34+ in monolayer c72fe245.
• The delivery effect is seen only across papers or with confounds. Meng 2012 compares lentivirus (up to 2% of transduced cells) with episomal delivery (about 20 colonies from the progeny of 100,000 cells) on one cord-blood CD34+ fraction, but input number, pre-culture and vector design differ f81213bf.
• Spread on the same axis. For the adult-blood CD34+ versus bulk contrast, the reported gain ranges from about 33-fold (Okumura) to overlapping ranges (Ye), with Mack in between. These are not matched comparisons: donors, vectors, scoring day and pre-culture differ, so they are separate quantities and the corpus does not say which factor drives the spread (see Methodology and Limitations).
• Clarification on the Mack figure. The "2 to 8 fold" belongs to Mack and is quoted from the paper in the verified record. The separate figure of about 10-fold per million cells plated and about 3-fold per original cell belongs to Su 2013, a different paper and a different comparison (T/B-depleted against whole PBMNC) 9df3c5b0. An earlier version of this synthesis was refused for this; the two papers are kept apart below.

Evidence

Fraction varied, one delivery class

• Okumura et al. 2019 — SeVdp(KOSM)-302L Sendai, one healthy donor: bulk PBMC 0.17%, CD34-negative flow-through 0%, CD34+-enriched 5.58% (781 colonies from 14,000 cells), colonies at day 7 per seeded cell. Across 15 patients CD34+ efficiency ranges 0.08% to 3.26% with no bulk arm. No statistical test in the passages read. b8583100
• Ye et al. 2013 — CytoTune Sendai, two donors per fraction: CD34+ 0.05%-0.06% and MNC 0.02%-0.27%, TRA-1-60 and morphology on day 20. Pre-culture differs: CD34+ 2 days, MNC 5-8 days in different cytokines. The denominator is not stated in the readable text. 9b19c845
• Mack et al. 2011 — episomal oriP/EBNA1 plasmids, 10 donors, Wilcoxon signed-rank p=0.007: about 2 to 8-fold more colonies per input cell from CD34+-purified cells in 9 of 10 donors. The arms used their own expansion media. CD34-depleted cells were not receptive. Scoring day not stated. e3bddedb
• Su et al. 2013 — episomal OS+MK+BCL-XL, n=4 donors, P<0.05: T/B-depleted PBMNC gave about 10-fold more colonies per million cells plated and about 3-fold per original cell. With lentivirus, adult PBMNC reached 0.02% (OS) and 0.2% (OS+MK) against 1-2% for cord-blood CD34+. No same-fraction lentivirus-versus-episomal percentage comparison. 9df3c5b0
• Liu et al. 2015 — one episomal electroporation method: up to 0.033% (65 colonies from 200,000 MNC) against 0.148% (148 colonies from 100,000 cord-blood or fetal-liver CD34+ cells), about 4.5-fold. The MNC figure is a best value, fraction covaries with tissue and age, and only the abstract was read. ce0f63cb
• Kuebler et al. 2025 — bank-wide retrospective dataset, Sendai: cord-blood CD34+ 1.199% (n=10 lines) against PBMC 0.015% (n=57 lines), p<0.0001, about 80-fold. Source (cord against adult), kit version and handling are confounded with fraction. 2c8fedc1
• Muñoz-López et al. 2016 — Sendai OSKM: fetal-liver CD34+CD19+ progenitor B cells 0.46% against 0.11% for mature B cells; fetal-liver B cells 110-fold easier than cord or peripheral-blood B cells, an ontogeny contrast. Abstract only. 64a6f8aa
• Chou et al. 2011 — episomal EBNA1/OriP: unfractionated MNC under CD34+ conditions gave zero colonies per 5 million MNC; cultured adult PB MNC 3.2 per 2 million cells (about 14 with a second plasmid); adult PB/BM CD34+ about 50-fold lower than cord-blood CD34+. Vector or additive changes moved yields about 3-5-fold. Counts, not percentages. 5a3fbe25
• Lam et al. 2022 — CytoTune 2.0 Sendai, TRA-1-60 at day 14 per initial cell, n=3. Monolayer: PBMC 0.02 ± 0.01%, CD3+ 0.02 ± 0.001%, CD34+ 0.02 ± 0.01%. Microcarriers: PBMC 0.97 ± 0.1%, CD3+ 0.85 ± 0.05%, CD34+ 0.5 ± 0.1%. Culture format, a third axis, moves the number 47.6 ± 7.5-fold for PBMC, 41.3 ± 3.7-fold for CD3+ and 36.4 ± 9.2-fold for CD34+; significance marks compare formats, not fractions. The format arms also change substrate, agitation and medium. c72fe245
• Zhou et al. 2015 — Sendai on 4-day cytokine-expanded PBMC only: 0.15% to 0.32% TRA-1-60+ at day 10. One fraction, one class, so not a comparison; no order-of-magnitude gain from expansion against bulk-PBMC figures elsewhere. 36d39357
• Watanabe et al. 2018 — zoledronate/IL-2-stimulated whole PBMC with Sendai; one fraction, one class, no percentage printed. A not-stated row. 381a62c6

Delivery class varied

• Meng et al. 2012 — cord-blood CD34+, same SFFV-OCT4/SOX2 cassette: lentiviral up to 2% of transduced cells; episomal about 20 colonies from the progeny of 100,000 cells (about 0.02%, computed in the record). Input number, pre-culture and vector design differ; no fraction arm. f81213bf
• Merling et al. 2013 — the one paper with both axes. Delivery: the same CD34+-enriched blood sample gave 7 TRA-1-60+ colonies from 14 mL with the STEMCCA-loxP lentivector and more than 120 from 6 mL with Sendai, more than 40-fold per mL of blood, at different MOI and counted per mL, not per input cell. Fraction: CD14+ monocytes gave no clone with the lentivector, while mobilized CD34+ gave 4/20,000, 10/50,000 and 4/50,000. The matched delivery comparison is n=1 donor. f925d777

Multi-paper search record

• Search of 2026-10-13 (Okumura, Loh 2010, Kuebler, Hamada 2020, Lam, Staerk 2010) — Loh: lentivirus, CD34+ 0.002% against PBMC 0.0008-0.001%, about 2- to 2.5-fold with different infection schedules. Hamada: Sendai, PBMC pre-cultured 0, 3 and 6 days gave 0.024%, 0.051% and 0.0033%, about 15-fold between 3 and 6 days. Staerk: overall blood efficiency 0.001-0.0002% with no quantitative fraction contrast. No paper found that ranks both axes. fc8b5066

Methodology

Every verified fact of the task is used. Each paper is kept as its own row with its fractions, delivery classes, scoring and denominator; the platform lists no measurement conflicts, and nothing is pooled across papers because cell source, vector, marker, day and denominator differ. Fold-changes are those printed in the records, or those a record computed from printed numbers, and are used only inside their own paper. Papers were separated into those that vary the fraction under one class, those that vary the class on one fraction, and those that vary neither. Cord-blood or fetal-liver against adult contrasts are treated as ontogeny contrasts and kept apart from adult-blood sub-population contrasts. Handling (pre-culture duration, activation, culture format) is treated as a third axis. This synthesis ran no new literature search; negatives refer to the searches documented in the facts.

Limitations

• No verified paper ranks delivery-class and starting-fraction effects in a matched percentage design. Merling comes closest but is n=1 for the delivery comparison, with different MOI and a per-mL denominator f925d777; Meng has a delivery arm but no fraction arm f81213bf.
• The Okumura fraction effect rests on one donor and the Ye ranges on two donors per fraction, with pre-culture differing between arms b8583100; 9b19c845.
• Several large contrasts mix tissue ontogeny with fraction 2c8fedc1; 64a6f8aa; 5a3fbe25.
• Liu and Muñoz-López are abstract-level records; Ye's Table 1 body did not render ce0f63cb; 64a6f8aa; 9b19c845.
• Lam's format effect cannot be assigned to vessel, substrate or agitation alone, and its fraction-isolation supplement was not read c72fe245.
• Zhou and Watanabe each use one fraction and one class, and Watanabe prints no efficiency percentage 36d39357; 381a62c6.
• Loh, Hamada and Staerk were read in the main text only, with replicates mostly not stated, and Loh's arms were handled differently fc8b5066.

Disposition of the inherited hypothesis

The earlier version's hypothesis (adult peripheral-blood enrichment gives less than tenfold, with larger gaps only across tissue sources) is not carried forward. Its own refutation condition names a paper in which cord or fetal versus adult arms differ by less than tenfold, and Liu 2015 reports about 4.5-fold for that contrast ce0f63cb. Its adult-blood arm also sits uneasily with Okumura's 33-fold gain in one donor, although the two use different vectors and scoring days b8583100. A successor is stated in the structured hypothesis field.