Lecture 13: Mesenchymal stem cells and other tissue stromal cells

A small piece of bone that is formed when mesenchymal stem cells (MSCs) are transplanted into a living organism.

An increase in fat cells within the bone marrow that occurs with age. This process can negatively impact hematopoiesis (blood cell production) and bone repair.

A process by which fat cells in the bone marrow suppress the production of blood cells.

A type of medication that inhibits the formation of fat cells. It can be used to enhance hematopoietic recovery after stem cell transplantation.

A decrease in the ability of MSCs to produce bone with age, which contributes to a shift towards increased fat and decreased bone formation.

A type of marker protein found on the surface of MSCs. An increase in these markers in aged mice indicates changes in the MSC population with aging.

The reduced ability of aged MSCs to form colonies of fibroblasts, indicating a decrease in their ability to differentiate into various cell types.

Mesenchymal stem cells (MSCs) play a crucial role in regulating hematopoiesis, the process of blood cell formation. They contribute to the hematopoietic stem cell (HSC) niche, which is the microenvironment within the bone marrow where HSCs reside, maintain self-renewal, and differentiate into various blood cell types. MSCs interact with HSCs through cell-cell communication, cytokine signaling, and extracellular matrix interactions, influencing their fate and function.

Aged MSCs exhibit a decline in their ability to support HSC function. This decline is characterized by reduced expression of essential genes required for HSC maintenance, including CXCL12, Stem Cell Factor, and Angiopoietin. CXCL12 is a chemokine that attracts HSCs to their niche, Stem Cell Factor is a growth factor that promotes HSC proliferation, and Angiopoietin is a signaling molecule that promotes blood vessel formation.

Aged MSCs display altered differentiation potential, leading to an imbalance in the production of different cell types. Specifically, they show a decreased capacity to generate bone cells and an increased tendency to produce fat cells. This shift in differentiation patterns negatively affects HSC engraftment and overall hematopoiesis.

The bone marrow is the principal site of adult hematopoiesis, where blood cells are generated from hematopoietic stem cells (HSCs). It also houses the specific microenvironment called the HSC niche, which provides the necessary support for HSC self-renewal and differentiation.

The HSC niche is a specialized microenvironment within the bone marrow that serves as a home for hematopoietic stem cells (HSCs). This niche provides all the essential factors, including cell-cell interactions, cytokines, chemokines, growth factors, and extracellular matrix components, to regulate HSC maintenance and differentiation.

Hematopoietic stem cells (HSCs) possess a remarkable ability to self-renew and differentiate into all types of blood cells, including red blood cells, white blood cells, and platelets. This process of blood cell production from HSCs is called hematopoiesis.

Aged HSCs, compared to their younger counterparts, exhibit several functional changes. They mobilize more readily into circulation but show reduced effectiveness in repopulating the bone marrow. They also display a bias toward the myeloid lineage, resulting in a decreased production of lymphoid cells.

Homing, in the context of HSCs, describes the process by which these cells migrate to and establish themselves within their specific niche in the bone marrow. This process is crucial for HSC engraftment after transplantation and during normal circulation, as it ensures that HSCs return to their proper location to support blood cell production.

The location of HSCs within the bone marrow influences their function. Younger HSCs typically reside closer to the endosteum, the inner lining of bone, whereas aged HSCs tend to be found further away from this region. This change in distribution can affect HSC homing and overall function.

Stromal cells in adipose tissue providing structural support and regulating immune homeostasis.

The stromal vascular fraction (SVF) is a component of lipoaspirate, containing ADSCs, hematopoietic cells, preadipocytes, endothelial cells, and pericytes.

While ADSCs lack in vivo multipotency and self-renewal, they play a crucial role in immune regulation.

ADSCs are the main source of IL-33, an alarmin crucial for immune cell function and expansion.

IL-33 plays a key role in supporting the function and expansion of T cells, innate lymphoid cells (ILCs), and macrophages.

Aging leads to an accumulation of ADSCs, resulting in increased IL-33 levels, leading to expansion of adipose Tregs and potential metabolic complications.

Sex differences exist in ADSC function, with males having a higher number of IL-33-producing ADSCs and increased adipose Tregs.

The increased IL-33 and adipose Tregs in males may predispose them to obesity-induced inflammation and insulin resistance.

ADSCs play a key role in supporting various immune cell types, contributing to overall immune homeostasis.

While ADSCs are not true stem cells, they are essential for the immune regulation of adipose tissue and play a role in metabolic health.

The thymus is divided into two main regions: the outer cortex and the inner medulla, each with specific functions and cell types.

Epithelial cells, mesenchymal cells (fibroblasts), endothelial cells, and neuroendocrine cells are all found in the thymus. They play critical roles in supporting and regulating the development of T cells.

The interaction between stromal cells and developing thymocytes, known as thymic cross-talk, is essential for T cell development and maturation. Stromal cells provide signaling molecules and create specific environments that guide T cell differentiation.

As thymocytes migrate through different regions of the thymus, they encounter distinct stromal cell populations which provide specialized growth factors and cytokines that guide their development.

T cell development and maturation depend on the specific growth factors and cytokines provided by stromal cells. Conversely, thymocytes also influence the development and maintenance of the thymic epithelium.

Lymph nodes filter lymph fluid, trapping antigens and immune cells, which then activate lymphocytes and initiate an immune response.

Fibroblastic reticular cells (FRCs) are stromal cells found in lymph nodes. They provide structural support, guide fluid flow, and release signaling molecules that influence immune cell behavior.

The thymus is the primary site of T cell development, ensuring the production of mature and functional T cells essential for immune responses.

The thymus is a bilobed organ located in the chest, behind the sternum and in front of the heart. It has numerous lobules separated by connective tissue called trabeculae.

DiGeorge syndrome is a genetic condition where individuals lack a functional thymus, leading to a deficiency in T cells and compromised immunity.

Lymph nodes are organized structures with distinct compartments. B cells reside in follicles, T cells in the paracortex, and macrophages and plasma cells in the medulla.

Lymph fluid carries antigens, soluble mediators, and antigen-presenting cells from peripheral tissues to lymph nodes, initiating immune responses.

FRCs produce chemokines and cytokines that attract and support immune cells, influencing their migration and survival within the lymph nodes.

FRCs create channels within lymph nodes called conduits, facilitating the flow of lymph, chemokines, cytokines, and antigens.

The thymus is crucial for immune function because its absence leads to a lack of T cells, resulting in immunodeficiency.