Discovery of aging mechanism for hematopoietic stem cells

©Atsushi IWAMA, The Institute of Medical Science, The University of Tokyo

By transferring mouse aged hematopoietic stem cells (aged HSCs, *1) to the environment of young mice (bone marrow niche, *2), it was demonstrated that the pattern of stem cell gene expression was rejuvenated to that of young hematopoietic stem cells. On the other hand, the function of aged HSCs did not recover in the young bone marrow niche. The epigenome (DNA methylation, *3) of aged HSCs did not change significantly even in the young bone marrow niche, and DNA methylation profiles were found to be a better index than the gene expression pattern of aged HSCs.

A research group led by Professor Atsushi Iwama at the Division of Stem Cell and Molecular Medicine, The Institute of Medical Science, The University of Tokyo (IMSUT) announced these world-first results and was published in the Journal of Experimental Medicine (online) on November 24th.

“The results will contribute to the development of treatments for age-related blood diseases,” states lead scientist, Professor Iwama at IMSUT.

Focus on changes in aged HSCs in the bone marrow niche

The research group investigated whether rejuvenating aged HSCs in a young bone marrow niche environment would rejuvenate.

Tens of thousands of aged hematopoietic stem/progenitor cells collected from 20-month-old mice were transplanted into 8-week-old young mice without pretreatment such as irradiation. After two months of follow-up, they collected bone marrow cells and performed flow cytometric analysis.

The research team also transplanted 10-week-old young mouse HSCs for comparison. In addition, engrafted aged HSCs were fractionated and RNA sequence analysis and DNA methylation analysis were performed.

They found that engrafted aged HSCs were less capable of producing hematopoietic cells than younger HSCs. They also showed that differentiation of aged HSCs into multipotent progenitor cells was persistently impaired even in the young bone marrow niche, and that the direction of differentiation was biased. It was found that the transfer of aged HSCs to the young bone marrow niche does not improve their stem cell function.

A more detailed analysis may reveal mechanisms that irreversibly affect aged HSC function

Aging studies focusing on HSCs have been actively pursued in mice using a bone marrow transfer model. However, the effect of aging on HSCs remains to be clarified.

Professor Iwama states as follows.”This study has a significant impact because it clarified the effect of aging on HSCs. Our results are expected to contribute to further elucidation of the mechanism of aging in HSCs and understanding of the pathogenic mechanism of age-related blood diseases.”

National Cord Blood Awareness Month – Why are medical conditions can be treated with cord blood?


Stem cells

Stem cells

In the three years (or so) since this blog was founded we have run a number of articles on on stem cell treatments. And , in particular, on cord blood which contains stem cells.

The most common, and original, type is bone marrow transplant.

In our original post of stem cell therapy we explained that “Stem cell therapy is where doctors introduce adult stem cells into damaged tissue which in turn helps to treat an injury or disease. …So what is a stem cell? You have to sift through a lot of waffle on the internet to find out the answer but, in a nutshell, they are cells which have the ability to become other cells. They are a sort of “mother cell” which is not directly linked to a specific bodily function but can turn into, say, blood or bone cells. In scientific parlance stem cells are undifferentiated cells as opposed to say muscle cells which are referred to as differentiated.These stem cells are often cultivated in a lab and then transplanted to the host/patient as a treatment. The cells may help generate new cells which can affect a cure. One example is that stem cells may be used to kick start insulin production in the pancreas as a way of treating T1 diabetes.

The purpose of this blog post if to look at a number of conditions which can be treated. We looked at multiple sclerosis in a previous blog which you might wish to read here.


It is worth mentioning that given the nature of the treatment many of the conditions which are currently treated relate to blood cancers.

Acute Leukemia’s – which can include :-
Acute Lymphoblast Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Acute Biphenotypic Leukemia
Acute Undifferentiated Leukemia

Chronic Leukemia’s – such as:-

Chronic Myelogenous Leukemia (CML)
Chronic Lymphocytic Leukemia (CLL)
Juvenile Chronic Myelogenous Leukemia (JCML)
Juvenile Myelomonocytic Leukemia (JMML)

Myelodysplastic Syndromes

Refractory Anemia (RA)
Chronic Myelomonocytic Leukemia (CMML)

Stem Cell Disorders

Aplastic Anemia
Fanconi Anemia
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Pure Red Cell Aplasia

Myeloproliferative Disorders

Acute Myelofibrosis
Agnogenic Myeloid Metaplasia (myelofibrosis)
Polycythemia Vera
Essential Thrombocythemia

Phagocyte Disorders

Chediak-Higashi Syndrome
Chronic Granulomatous Disease
Neutrophil Actin Deficiency
Reticular Dysgenesis

Other Inherited Disorders

Lesch-Nyhan Syndrome
Cartilage-Hair Hypoplasia
Glanzmann Thrombasthenia
Osteopetrosis
Adrenoleukodystrophy

Other Malignancies

Ewing Sarcoma
Neuroblastoma
Renal Cell Carcinoma
Retinoblastoma

Sickle Cell Disease

Inherited Immune System Disorders

Ataxia-Telangiectasia
Kostmann Syndrome
Leukocyte Adhesion Deficiency
DiGeorge Syndrome
Bare Lymphocyte Syndrome
Omenn’s Syndrome
Severe Combined Immunodeficiency (SCID)
SCID with Adenosine Deaminase Deficiency
Absence of T & B Cells
Common Variable Immunodeficiency
Wiskott-Aldrich Syndrome
X-Linked Lymphoproliferative Disorder

Plasma Cell Disorders

Multiple Myeloma
Plasma Cell Leukemia
Waldenstrom’s Macroglobulinemia
Amyloidosis

Lymphoproliferative Disorders

Non-Hodgkin’s Lymphoma
Hodgkin’s Disease

It is worth mentioning that some research has been conducted look at stem cell treatments for autism. But this is still both experimental and controversial.

Finally over to you. Have you ever had stem cell treatments or a bone marrow transplant? If so please tell us a bit more in the comments section below.

Many thanks in advance.