reprogramming-mouse-embryonic-fibroblasts-with-transcription-factors

Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program

This protocol details the induction of a hemogenic program in mouse embryonic fibroblasts (MEFs) via overexpression of transcription factors (TFs). We ...

Icahn School of Medicine at Mount Sinai

Previous attempts to either generate or expand hematopoietic stem cells (HSCs) in vitro have involved either ex vivo expansion of pre-existing patient or donor HSCs or de novo generation from pluripotent stem cells (PSCs), comprising both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). iPSCs alleviated ESC ethical issues but attempts to generate functional mature hematopoietic stem and progenitor cells (HSPCs) have been largely unsuccessful. New efforts focus on directly reprogramming somatic cells into definitive HSCs and HSPCs. To meet clinical needs and to advance drug discovery and stem cell therapy, alternative approaches are necessary. In this review, we synthesize the strategies used and the key findings made in recent years by those trying to make an HSC.

Making a Hematopoietic Stem Cell.

The Orphan Drug Act has fostered drug development for patients with rare cancers and other diseases; however, current data suggest that companies are gaming the system to use the law for mainstream drugs. We identify a pattern of pharmaceutical companies submitting drugs to the Food and Drug Administration (FDA) as orphan drugs but once approved, the drugs are used broadly off-label with the lucrative orphan drug protections and exclusivity benefits. Since the law was passed, the proportion of new FDA-approved drugs that were submitted as orphan drugs has increased with a peak last year of 41% of all FDA-approved drugs approved as orphan drugs. On the basis of the current data, we suggest that patients with rare cancers and other diseases may suffer due to dilution of the incentives and benefits. We propose reform to increase submission scrutiny, decrease benefits based on off-label use, and increase price transparency.

The Orphan Drug Act: Restoring the Mission to Rare Diseases.

Even though all paradigms of stem cell therapy and regenerative medicine emerged from the study of hematopoietic stem cells (HSCs), the inability to generate these cells de novo or expand them in vitro persists. Initial efforts to obtain these cells began with the use of embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) technologies, but these strategies have yet to yield fully functional cells. Subsequently, more recent approaches involve transcription factor (TF) overexpression to reprogram PSCs and various somatic cells. The induction of pluripotency with just four TFs by Yamanaka informs our ability to convert cell fates and demonstrates the feasibility of utilizing terminally differentiated cells to generate cells with multilineage potential. In this review, we discuss the recent efforts undertaken using TF-based reprogramming strategies to convert several cell types into HSCs.

Converting cell fates: generating hematopoietic stem cells de novo via transcription factor reprogramming.

The review examines the utility of stem cell biology in ophthalmology and oculoplastic surgery.

Michael G. Daniel

Department of Developmental and Regenerative Biology,
The Graduate School of Biomedical Science,
Black Family Stem Cell Institute

Icahn School of Medicine at Mount Sinai

Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program

Michael G. Daniel

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Developmental and Regenerative Biology,The Graduate School of Biomedical Science,Black Family Stem Cell Institute

Icahn School of Medicine at Mount Sinai

Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program

Department of Developmental and Regenerative Biology,
The Graduate School of Biomedical Science,
Black Family Stem Cell Institute