Printer Friendly

New technique raises possibility of making all types of blood cells.

BOSTON, Mass., May 17, 2017 -- Researchers at Boston Children's Hospital have for the first time generated blood forming stem cells in the lab using pluripotent stem cells that can make virtually every cell type in the body.

The advance opens new avenues for research into the root causes of blood diseases and to creating immune matched blood cells for treatment purposes, derived from patients' own cells.

The researchers said they are close to generating bona fide human blood stem cells in a dish.

"This work is the culmination of over 20 years of striving," said senior investigator George Daley of Harvard Medical School.

Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they proved capable of generating multiple types of human blood cells when put into mice.

This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells.

It also has the potential to provide a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions.

Since human embryonic stem (ES) cells were isolated in 1998, scientists have been trying, with little success, to use them to make blood forming stem cells.

In 2007, three groups (including the Daley lab) generated the first induced pluripotent stem (iPS) cells from human skin cells through genetic reprogramming.

iPS cells were later used to generate multiple human cell types, such as neurons and heart cells. But blood forming stem cells remained elusive.

The researchers combined two previous approaches. First, they exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals that direct stem cells to differentiate into specialized cells and tissues during normal embryonic development.

This generated hemogenic endothelium, an early embryonic tissue that eventually gives rise to blood stem cells, although the transition to blood stem cells had never been achieved in a dish.

In the second step, the team added genetic regulatory factors (called transcription factors) to push the hemogenic endothelium toward a blood forming state.

Starting with 26 transcription factors identified as likely candidates, they eventually came down to just five (RUNX1, ERG, LCOR, HOXA5 and HOXA9) that were both necessary and sufficient for creating blood stem cells.

They delivered the factors into the cells with a lentivirus, as used in some forms of gene therapy.

Lastly, they transplanted the genetically engineered hemogenic endothelial cells into mice. Weeks later, a small number of the animals carried multiple types of human blood cells in their bone marrow and blood circulation.

These included red blood cell precursors, myeloid cells (precursors of monocytes, macrophages, neutrophils, platelets and other cells), and T and B lymphocytes.

Some mice were able to mount a human immune response after vaccination.

ES cells and iPS cells were similarly good at creating blood stem and progenitor cells when the technique was applied.

But the researchers are most interested in iPS cells, which offer the added ability to derive cells directly from patients and model disease.

"We're now able to model human blood function in so called 'humanized mice,'" said Daley. "This is a major step forward for our ability to investigate genetic blood disease."

The researchers' technique produced a mixture of blood stem cells and hematopoietic progenitor cells, which also give rise to blood cells. The ultimate goal is to expand their ability to make true blood stem cells in a way that's practical and safe, without the need for viruses to deliver the transcription factors, and to introduce gene-editing techniques like CRISPR to correct genetic defects in pluripotent stem cells before blood cells are made.

One challenge in making bona fide human blood stem cells is that no one's been able to fully characterize these cells.

Citation: Ryohichi Sugimura et al., "Hematopoietic stem and progenitor cells from human pluripotent stem cells," Nature, May 2017 DOI: 10.1038/nature22370

Abstract/Article: http://bit.ly/2rtPHu4

Contact: George Q. Daley, george. daley @childrens. harvard.edu
COPYRIGHT 2017 DataTrends Publications, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2017 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Advanced Stem Cell Technology
Publication:Stem Cell Business News
Date:May 29, 2017
Words:687
Previous Article:New protocol for deriving microglia from human stem cells.
Next Article:Self-renewing hematopoietic stem cells created for transplantation.
Topics:

Terms of use | Privacy policy | Copyright © 2022 Farlex, Inc. | Feedback | For webmasters |