Bone Marrow Aging Linked to Aging of Blood Cell Forming Stem Cells

Hematopoietic stem cells (HSCs) are found to age as people age, resulting in higher risk for certain types of blood cancer and an elevated risk for lowered immunity. A study published in the journal EMBO has shown that a section of the bone marrow where hematopoietic stem cells are formed, also age, aggravating the risk for the disease. A research team from the University of Ulm (Germany) along with scientists from Cincinnati Children’s Hospital Medical Center(United States)have stated that rejuvenating the section of the bone marrow where hematopoietic stem cells are formed would ensure

• Younger hematopoietic stem cells which result in healthier blood cells
• Increased immunity among older people
• A more potent defense response against some types of blood cancer

The study was conducted on mice, specifically on a group of stem cells that lead to the development of bone, osteoblasts.  A protein called osteopontin produced by the osteoblasts is necessary for the healthy environment of the bone marrow which is imperative for the production of blood cells from hematopoietic stem cells.

Dr. Hartmut Geiger said that the studies conducted showed that the niche where the hematopoietic stem cells are formed lacks the osteopontin with advancement in age but a restoration of the level of these proteins showed that the blood cells produced were younger. The lead author of the study further claimed that the study aided in pointing towards better forms of therapy for poor immunity and could be used to develop potential therapy for blood cancer. The study, though conducted on mice, indicates a possible new line of research.

Bone Marrow Aging

The research team was involved in numerous experiments to identify a method to determine blood cell development as well as the vitality of the cells that were present in the microenvironment of the bone marrow. One of the experiments that were conducted involved the development of the endosteum stroma cells that give rise to a thin layer of connective tissue present on the interior side of the bones. The levels of proteins that were associated with specific cells in the bone marrow, like osteopontin, were monitored to understand the aging of the bone marrow.

The findings of these experiments were

• Older mice exhibited lowered osteoblasts and other stroma cell production in the endosteum.
• There were lowered osteopontin levels in the bone marrow also among older mice, which was displayed by reduction in the function as well as the vigor of hematopoietic stem cells.

Setting Right The Aging of Bone Marrow

The research team modified the previous studies and conducted further studies on

• Transplanting bone marrow cells from 19-21 months (older) mice into 8 to 10 weeks (young) mice.
• The mice were treated with a recombinant variant of the osteopontin protein

The experiment that involved transplanting the bone marrow from older mice to the younger mice resulted in

• The cells of  the younger mice to behave in a more vital manner.
• There were a fewer number of hematopoietic stem cells which had the ability to transform into various types of blood cells.
• The blood cell types that were predominantly formed were T and B cells while the production of myeloid cells was low.

The experiment that involved treating the hematopoietic stem cells with osteopontin resulted in

• Younger cells that showed the potential to develop into various types of blood cells.
• Reduced Cdc42 signaling, a protein that was shown to induce aging of the hematopoietic stem cells

The levels of the protein Osteopontin were not only found to be low in the section of the bone marrow where hematopoietic cells were formed, but were also detected in the aging blood. The study has prompted the scientists into studying if osteopontin replacement therapy could be used to reverse the signs of aging in the hematopoietic stem cells.

Difference Between Aging Hematopoietic Stem Cells (HSC) and Young HSC Cells

In a study conducted by Morrison and colleagues titled “The aging of hematopoietic stem cells.” And published in the journal Nature Medicine, the purified hematopoietic stem cells (HSCs) which were extracted from the bone marrow of old mice were compared with the hematopoietic stem cells mice that were young. The study showed that

• The hematopoietic stem cells in the mice, both young and old, were found to be similar.
• There was more frequency of hematopoietic stem cells in older mice than in young mice- 5 times more.
• Life Cycle of the Cell - The hematopoietic stem cells from older mice were from M/S/G2 phases of the cell cycle, but the hematopoietic stem cells from young mice were rarely found in these phases.

There was a marked difference in the functioning of the hematopoietic stem cells as they grew older along with the age of the animal. The current study that identified a potential means of therapy or rejuvenating techniques which could reverse aging will aid in increasing host immune defenses as well as better control mechanism against cancer. 

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References:

1. Novella Guidi, Mehmet Sacma, Ludger Ständker, Karin Soller, Gina Marka, Karina Eiwen, Johannes M Weiss, Frank Kirchhoff, Tanja Weil, Jose A Cancelas, Maria Carolina Florian, Hartmut Geiger. Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells. EMBO, 2017 DOI: 10.15252/embj.201694969
2. The aging of hematopoietic stem cells - (https://www.ncbi.nlm.nih.gov/pubmed/8782459)

Source-Medindia