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Record W2019329770 · doi:10.1006/mthe.2002.0583

Characterization of Retroviral Gene Transfer into Highly Purified Human CD34− Cells with Primitive Hematopoietic Capacity

2002· article· en· W2019329770 on OpenAlexaff
Barbara Murdoch, Lisa Gallacher, Kristin Chadwick, Mickie Bhatia

Bibliographic record

VenueMolecular Therapy · 2002
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicVirus-based gene therapy research
Canadian institutionsRobarts Clinical TrialsWestern University
Fundersnot available
KeywordsCD38HaematopoiesisBiologyCD34Molecular biologyProgenitor cellStem cellTransduction (biophysics)Cell biologyBiochemistry

Abstract

fetched live from OpenAlex

Primitive human hematopoietic cells have recently been identified within a rare subfraction of CD34− lineage-depleted (Lin−) cells and further characterized by their restriction to a rarer subset expressing AC133. Here we show that CD34−AC133+Lin− cells can be transduced by retrovirus at a comparatively higher efficiency than either CD34−AC133−Lin− or CD34+CD38−Lin− cells. Subpopulations were transduced by enhanced green fluorescent protein (eGFP)-containing retrovirus in serum-free conditions. During the culture period, both CD34−AC133+Lin− and CD34+CD38−Lin− subfractions expanded, whereas CD34−AC133−Lin− cells could not be sustained. Fluorescent microscopic examination of progenitors assayed by colony-forming units (CFU) derived from CD34−AC133+Lin− cells revealed expression of eGFP, with the presence of provirus confirmed by clonal PCR analysis. Flow cytometry detecting eGFP revealed that cultures seeded with CD34−AC133+Lin− cells had a greater than threefold higher frequency of eGFP+ cells compared with transduced cultures of CD34+CD38−Lin− cells. Our results demonstrate that retroviral transduction efficiency and level of transgene expression into CD34−AC133+Lin− cells is distinct to either CD34−AC133−Lin− or CD34+CD38−Lin− cells. This study represents the first evaluation of retroviral transduction into this population of primitive CD34− cells, and therefore provides the basis for optimization of gene transfer protocols to examine the role of gene-marked CD34− stem cells in a clinical setting. Primitive human hematopoietic cells have recently been identified within a rare subfraction of CD34− lineage-depleted (Lin−) cells and further characterized by their restriction to a rarer subset expressing AC133. Here we show that CD34−AC133+Lin− cells can be transduced by retrovirus at a comparatively higher efficiency than either CD34−AC133−Lin− or CD34+CD38−Lin− cells. Subpopulations were transduced by enhanced green fluorescent protein (eGFP)-containing retrovirus in serum-free conditions. During the culture period, both CD34−AC133+Lin− and CD34+CD38−Lin− subfractions expanded, whereas CD34−AC133−Lin− cells could not be sustained. Fluorescent microscopic examination of progenitors assayed by colony-forming units (CFU) derived from CD34−AC133+Lin− cells revealed expression of eGFP, with the presence of provirus confirmed by clonal PCR analysis. Flow cytometry detecting eGFP revealed that cultures seeded with CD34−AC133+Lin− cells had a greater than threefold higher frequency of eGFP+ cells compared with transduced cultures of CD34+CD38−Lin− cells. Our results demonstrate that retroviral transduction efficiency and level of transgene expression into CD34−AC133+Lin− cells is distinct to either CD34−AC133−Lin− or CD34+CD38−Lin− cells. This study represents the first evaluation of retroviral transduction into this population of primitive CD34− cells, and therefore provides the basis for optimization of gene transfer protocols to examine the role of gene-marked CD34− stem cells in a clinical setting.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.240
Teacher spread0.222 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7
Published2002
Admission routes1
Has abstractyes

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