Stemness of primary AMSC lines demonstrated with differentiation along three mesenchymal lineages, Adipocyte (a, d , g), Osteocyte (b , e, h), and Chondrocyte (c , f, i), documented via lineage specific staining with Oil Red O, Alizarin Red, and Collagen II, respectively. (Credit: Pendleton et al. Mesenchymal Stem Cells Derived from Adipose Tissue vs Bone Marrow: In Vitro Comparison of Their Tropism towards Gliomas. PLoS ONE, 2013; 8 (3): e58198 DOI: 10.1371/journal.pone.0058198)
Using Fat to Fight Brain Cancer: Stem Cells from Human Adipose Tissue Used to Chase Migrating Cancer Cells
Mar. 12, 2013 — In laboratory studies, Johns Hopkins researchers say they have found that stem cells from a patient’s own fat may have the potential to deliver new treatments directly into the brain after the surgical removal of a glioblastoma, the most common and aggressive form of brain tumor.
The investigators say so-called mesenchymal stem cells (MSCs) have…
Induced pluripotent stem cells (iPSCs) are made from adult cells by genetic manipulation. In short, four different genes, all of which encode DNA-binding proteins that direct gene expression, are introduced into adult cells. The four proteins direct a gene expression program that dedifferentiates a small proportion of the cells to become stem cells that greatly resemble embryonic stem cells.
These iPSCs have the capacity to differentiate into any cell type in the adult body, but there are particular cell types that have proven difficult for iPSCs to make. One of these is the blood cell-making stem cell that normally resides in bone marrow. This stem cells, the hematopoietic stem cell or HSC. Several different types of blood cells have been made from iPSCs, but, again, making HSCs from iPSCs has proven elusive.
A paper from the laboratories of Leslie Silberstein and Daniel Tenen at the Harvard Stem Cell Institute and Harvard Medical School has used a new approach to make HSCs from iPSCs. In this paper, Giovanni Amabile and colleagues injected undifferentiated HSCs into mice whose immune systems were compromised to prevent them from rejecting the implanted cells. The iPSCs formed tumors known as teratomas that contained a wide variety of cells types that included HSCs. Isolation of these HSCs from the teratomas produced pure cultures of HSCs that could be used to reconstitute the immune system of mice.
Isolation of HSCs from teratomas is actually rather easy, since very high-affinity antibodies can bind to the surfaces of HSCs and facilitate their isolation. Once isolated, Amabile and others used them to reconstitute the immune system of imunodeficient mice. This demonstrates that HSCs isolated in this manner are transplantable.
Embryonic stem cells can be converted to HSCs by co-culturing them with OP9 cells, a special mouse bone marrow-derived cell line. If iPSCs were injected into mice with OP9 cells, the number of HSCs they made in culture greatly increased.
The cells produced by the HSCs were evaluated for functionality, and the white blood cells made all the right molecules, ate bacteria like they should and also moved like white blood cells. Antibody making cells all made antibodies and T cells responded just as they should and made all the right molecules in response to stimulation. Thus, these HSCs were normal HSCs and produced blood cells that were completely normal from a functional perspective.
This technique could provide a way to make HSCs for human antibody production, drug screening, and, possibly, transplanation. Unfortunately, if these cells have been passed through an animal, there is no way they can be used for human treatments, since they might have picked up animal viruses and animal sugars on their surfaces. If these procedure could be refined to eliminate passing the iPSCs through an animal , then this technique could certainly be used to make transplantable HSCs for the treatment of human diseases of the blood.