What is the possibility of rheumatoid arthritis treatment?

of bone marrow The soft, spongy tissue in the center of most bones in the body.

The bone marrow is located in the central medullary cavity and is surrounded by a thin membrane called the bone marrow. endosteumBone marrow is hematopoiesisthe process of new blood cells formed through hematopoietic stem cell (HSC) division and differentiation.

Besides producing daughter HSCs after cell division, HSCs also produce different types of progenitor cells, which divide to produce specific types of mature blood cells. These mature blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), and cells belonging to the myeloid lineage.

Myeloid cells, in particular, include macrophages, platelets, monocytes, and granulocytes, some of which play important roles in generating immune responses.

bone marrow niche

In addition to housing hematopoietic stem cells and their progeny, the endosteum and central bone marrow contain cytokine Regulates HSC and progenitor cell formation, development, and function. All these cells, along with blood vessels and extracellular matrix, bone marrow niche.

The myeloid niche contains cells belonging to the stroma. mesenchymal stromal cells, adipocytes (adipocytes), nerve cells, connective tissue cells, and cells involved in bone formation and remodeling. Mesenchymal stromal cells can divide and differentiate into many cell types, including bone, cartilage, and adipocytes.

Bone marrow is abundant blood vessel, arteries, arterioles, capillaries, and sinusoids. Arteries transport oxygenated blood from the heart to smaller branches called arterioles, which then supply sinusoidal waves.

sine wave It is a special blood vessel with high permeability. The endothelial cells that form the lining of these blood vessels are also a major part of the bone marrow niche.

In this study, we found that myeloid niche cells that support HSC function play an important role in blood senescence.

Aging is associated with a decline in hematopoietic stem cell function. These changes in the hematopoietic system include a reduced ability of HSCs to generate new HSCs and progenitor cells, especially those that produce leukocytes.

These age-related changes can manifest as anemia, suppressed immune responses, increased susceptibility to disease, and even cancer.

Aging also affects the myeloid niche, but how these changes in the myeloid niche affect hematopoietic senescence has been poorly studied.

In the current study, the researchers performed several analyzes on hindlimb, forelimb, and pelvic bones from young and old mice to examine the effects of aging on interactions between the bone marrow niche and hematopoietic cells.

In this study, we found that the populations of mesenchymal stromal cells and osteoprogenitor cells involved in endosteal bone formation decreased in aged mice. In contrast, the central bone marrow of aged mice had increased numbers of mesenchymal stromal cells.

However, a significant fraction of these mesenchymal stromal cells in the central medullary space expressed inflammatory markers. In addition, there was loss of endothelial cells lining the sinusoids and changes in the sinusoidal vessels.

Further analysis of gene expression profiles in aged mice revealed increased expression of inflammatory genes across myeloid niche cells.

Increased inflammation in the bone marrow niche of aged mice was mediated by elevated expression and secretion of specific inflammatory cytokines, including IL-1β, by endosteal stromal cells.

Moreover, IL-1β secreted by endosteal stromal cells was sufficient to regulate the activity of HSCs.

“[We identified] Osteogenic ‘osteoprogenitor’ cells of the bone marrow niche are an unexpected source of inflammatory signals in aging animals, particularly IL-1. Surprisingly, using an FDA-approved drug for rheumatoid arthritis called anakinra, we were able to restore youthful blood production in aged mice by specifically blocking the effects of IL-1. ,” said the study authors. Dr. Emmanuel PassegDirector of the Columbia Stem Cell Initiative said:

“Consistently, aged animals genetically lacking cellular receptors for IL-1 had healthier niches and blood systems than unmodified animals. inhibiting is a useful strategy for maintaining efficient blood production in the elderly,” continues Dr. Pasge.

“More generally, it also provides a roadmap for identifying and harnessing specific biomolecules to improve tissue function during aging,” he added.

Increased niche inflammation in aged mice also adversely affected hematopoietic stem cells and their progeny.

Scientists have observed that increased niche cell inflammation is associated with increased ways that HSCs and progenitor cells differentiate into myeloid cells, such as macrophages and granulocytes, and platelet cells.

In contrast, the bone marrow of aged mice showed reduced differentiation of progenitor cells into the types of white blood cells, lymphocytes and erythrocytes.

Aged mice also showed impaired ability to regenerate hematopoietic stem and blood cells after exposure to 5-fluorouracil, a chemical that depletes dividing bone marrow cells.

These results suggest that age-related inflammation in the bone marrow niche also alters the hematopoietic compartment.

Research so far We show that treatment with the cytokine IL-1β can recapitulate the effects of senescence on hematopoietic cells.

Here, the researchers also found that IL-1β treatment mimicked the effects of aging on the bone marrow niche, including sinusoidal vascular changes and a decrease in endosteal stromal cell populations.

Furthermore, two weeks of treatment with the IL receptor blocker anakinra helped to attenuate the effects of 5-fluorouracil on hematopoietic cell regeneration in aged mice.

Genetically engineered mice lacking receptors for IL-1 signaling exhibit reduced levels of inflammatory mesenchymal stromal cells in the central bone marrow and limited loss of endosteal stromal cells after treatment with anakinra. , also showed a limited effect of aging on bone marrow niche composition.

Lifelong genetic inhibition of IL-1 signaling also reduced signs of blood senescence, but could not completely eliminate the effects of senescence. It showed decreased cell production, anemia, and decreased lymphocyte loss.

Taken together, these results suggest that IL-1 released by endomedullary stromal cells may play a role in causing inflammation in the myeloid niche and hematopoietic cells, ultimately leading to senescence of blood-producing cells. It suggests that

Notably, these results, pending human studies, suggest that inhibition of IL-1 signaling could be used to regenerate HSCs and their progenitor cells in the elderly, or after chemotherapy or other treatments leading to impaired hematopoiesis. suggesting that it is possible.

However, further studies are needed to improve hematopoietic regeneration using therapies that target IL-1 function.

“Our study was performed in mice, which share many features of blood aging with humans. To justify clinical trials, we focused on healthier blood production in elderly patients treated with anakinra.” Similar to epidemiology, further validation of our findings with human cells is needed,” said Dr. Passegue.