Lecture 13: Mesenchymal stem cells and other tissue stromal cells

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary consequence of increased adipocytes in bone marrow due to aging?

Increased osteogenic potential.

Greater formation of fibroblastic colonies.

Enhanced stem cell engraftment.

Suppressed hematopoiesis. (correct)

What signifies the ossicle created by MSCs during transplantation?

It contains a single type of stem cell.

It is composed of bone, adipocytes, and fibroblasts. (correct)

It is only formed by adipocytes.

It consists solely of fibroblasts.

Which intervention has been shown to potentially enhance hematopoietic recovery in aged mice?

PPAR Gamma Inhibition. (correct)

Increased MSC markers.

Reduction of fibroblasts.

Increased fatty degeneration.

What change occurs in the MSC population of aged mice?

Lower clonogenic potential. Signup and view all the answers

What impact does fatty degeneration have on stem cell transplantation?

It leads to reduced functionality of stem cells. Signup and view all the answers

What happens to MSC markers in aged mice according to the findings?

Increased PDGFRα and CD51-positive MSCs are observed. Signup and view all the answers

What is the overall effect of aging on MSC osteogenic potential?

It reduces the osteogenic potential. Signup and view all the answers

What are the two main regions of the thymus?

Outer Cortex and Inner Medulla Signup and view all the answers

Which type of cells is NOT part of the thymic stromal compartment?

Hematopoietic Cells Signup and view all the answers

What role do thymic stromal cells play during T cell development?

They provide growth factors and spatial cues. Signup and view all the answers

Thymic cross-talk refers to interactions between which two components?

Thymic stromal cells and developing thymocytes Signup and view all the answers

What is required for the development and maintenance of the thymic epithelium?

Interaction with thymocytes Signup and view all the answers

What is the impact of aged mesenchymal stem cells (MSCs) on hematopoietic stem cells (HSCs)?

Aged MSCs decrease the supportive capabilities of HSCs. Signup and view all the answers

Which of the following gene expressions is reduced in aged MSCs?

CXCL12 Signup and view all the answers

How do aged HSCs compare to young HSCs in terms of lineage output?

Aged HSCs are skewed toward myeloid lineage. Signup and view all the answers

What effect do increased adipocytes in aged MSCs have on HSCs?

Increased adipocytes negatively affect HSC engraftment. Signup and view all the answers

Which characteristic of aged HSCs is NOT mentioned?

Decreased number of HSCs. Signup and view all the answers

What is a crucial aspect of HSCs' function after transplantation?

Their ability to migrate and establish themselves in the bone marrow niche. Signup and view all the answers

Which of the following statements about the HSC niche is correct?

The HSC niche involves cell-cell contact, growth factors, and cytokines. Signup and view all the answers

What is one consequence of reduced levels of Cell Adhesion Molecules (CAMs) in aged HSCs?

Impaired migration to the bone marrow niche. Signup and view all the answers

Which factor is NOT involved in the regulation of HSCs within their niche?

Nutrient availability Signup and view all the answers

What is the primary role of adipose-derived stromal cells (ADSCs) in adipose tissue?

Providing structural support and regulating immune homeostasis Signup and view all the answers

Which component is isolated along with ADSCs from lipoaspirate during the separation process?

Stromal vascular fraction (SVF) Signup and view all the answers

In what way do ADSCs differ from true stem cells?

ADSCs lack in vivo demonstration of multipotency and self-renewal Signup and view all the answers

What role does interleukin 33 (IL-33) play in immune response?

It is essential for the function and expansion of various immune cells Signup and view all the answers

What is the impact of aging on adipose-derived stromal cells (ADSCs)?

Aging results in an accumulation of ADSCs and increased IL-33 levels Signup and view all the answers

How does the number of IL-33-producing ADSCs differ between sexes?

Males have a higher number than females Signup and view all the answers

Which immune cells are predominantly supported by IL-33 produced by ADSCs?

Regulatory T cells, innate lymphoid cells, and macrophages Signup and view all the answers

What metabolic conditions may result from the accumulation of ADSCs due to aging?

Metabolic abnormalities Signup and view all the answers

What predisposition is associated with the higher levels of adipose Tregs in males?

Increased likelihood of obesity-induced inflammation and insulin resistance Signup and view all the answers

What is the primary role of lymph nodes in the immune system?

Facilitate lymphocyte activation and immune response initiation. Signup and view all the answers

Where are B cells primarily located within the lymph node?

In the follicles. Signup and view all the answers

What condition is associated with a lack of functional T cells due to thymic absence?

DiGeorge syndrome. Signup and view all the answers

What is one of the main functions of fibroblastic reticular cells (FRCs) in lymph nodes?

Create conduits for the distribution of fluid and immune mediators. Signup and view all the answers

What component is NOT typically brought into lymph nodes by lymphatic drainage?

Neutrophils. Signup and view all the answers

Which of the following correctly describes the location of the thymus?

In front of the heart and between the lungs. Signup and view all the answers

What is a critical consequence of a lack of the thymus in the body?

Immunocompromised state due to T cell deficiency. Signup and view all the answers

In the organization of lymph nodes, where do macrophages reside?

In the medulla. Signup and view all the answers

What type of cells do fibroblastic reticular cells primarily support for immune function?

T cells. Signup and view all the answers

Which component is least likely to be actively involved in the immune response inside lymph nodes?

Red blood cells. Signup and view all the answers

Study Notes

Mesenchymal Stem Cells and Bone Marrow

Bone marrow is the primary site for hematopoiesis and B cell development in adults.
Bone marrow contains hematopoietic stem cells and stromal cells, which are embedded in a vascularized and innervated bone structure.
Bone marrow is distributed throughout the metaphysis, with projections called trabeculae.
The endosteum is the boundary between bone and marrow, lined by cells like osteoblasts and osteoclasts.
Osteoblasts are responsible for bone formation, and osteoclasts for bone resorption.

Bone Marrow Composition

Hematopoietic stem cells (HSCs) are responsible for blood cell formation (RBCs, WBCs, platelets).
The supportive stroma includes cells like fibroblasts (reticular connective tissue), macrophages (phagocytic cells), adipocytes (fat cells), osteoblasts (bone formation), osteoclasts (bone resorption), and endothelial cells (blood vessel formation).

Hematopoietic Stem Cell Niche

The HSC niche is the local microenvironment that maintains HSCs, controlling processes like rest, proliferation, self-renewal, and differentiation.
Communication in the niche occurs through cell-to-cell contact (adhesion molecules, gap junctions), cytokines and chemokines (e.g., CXCL12), and growth factors.
Extracellular matrix (ECM) components, like fibronectin, support the niche environment.
The niche comprises various cell types including mesenchymal stem cells (MSCs).

Role of MSCs in the Hematopoietic Stem Cell Niche

Mesenchymal stem cells (MSCs) express various factors (chemokines, growth factors, cytokines) crucial for maintaining HSC function.
MSCs are found in regions like perivascular locations (near blood vessels), central marrow, and endosteal regions (near bone surface).
MSCs are tightly linked with sympathetic nerve fibers, which have a role in regulating HSC mobilization.
Depletion of MSCs lowers HSC presence in the bone marrow.
Several populations of MSCs are found in various bone marrow anatomical regions, and different markers are expressed.

HSCs in Close Contact with MSCs

HSCs and MSCs are in close contact within the bone marrow microenvironment.
Not all MSCs are stem cells; their role is mainly supportive.
MSCs maintain HSCs, contribute to hematopoiesis, replenish osteoblasts and adipocytes, and can even produce cartilage under specific conditions.
MSCs must demonstrate the ability to generate fully differentiated tissues in vivo and reconstitute cells, in vivo, with identical phenotype and potency (as a test of their multipotency and self renewal).

Impact of Ageing

Ageing leads to increases in adipocytes in bone marrow, known as fatty degeneration.
This adipocyte accumulation affects HSC engraftment after stem cell transplantation and bone repair.
Bone marrow adipocyte deposits decrease hematopoiesis.
Ageing impacts MSC function and expression, decreasing osteogenesis, and producing fewer HSC-supporting factors.
In old mice, there are more MSCs but they show reduced ability to generate fully differentiated cells as well as in supporting HSC function.

Stromal Cells in the Lymphatic System

Lymph nodes are sentinels of the immune system, distributed throughout the body.
Lymph nodes allow lymphatic vessels to carry lymph to immune cells. Lymph contains antigens, soluble mediators, and antigen-presenting cells from peripheral tissues.
Lymph nodes have specialized structures (follicles, paracortex, medulla) to allow for interactions between lymphocytes, antigen presenting cells, and other cells.
Fibroblastic reticular cells (FRCs) maintain lymph node structure and function as conduits for fluid, chemokines, cytokines, and antigens. They produce chemokines and cytokines that support immune cell survival and trafficking.

Thymus

The thymus is the primary site for T cell development.
Absence of a thymus leads to immunodeficiency.
The thymus is a bilobed organ located behind the sternum, in front of the heart, and between the lungs.
The lobules of the thymus are separated by trabeculae, and the thymus has a cortex and medulla.
The thymic stromal compartment includes various cell types, including epithelial cells (cortex and medulla), mesenchymal cells/fibroblasts, endothelial cells, and neuroendocrine cells.

Thymic Cross-talk

Reciprocal interactions between thymic stromal cells and developing thymocytes (thymocytes are precursor T cells), called thymic cross-talk, are crucial for development and function in both compartments.
T cell development is guided by spatial cues provided by thymic stromal cells.
Development and maintenance of the thymic epithelium is dependent upon interactions with thymocytes.

Thymic T Cell Development

Bone marrow-derived precursors enter the thymus and migrate through the cortex to the subcapsular, cortical-medullary junction.
Thymocytes undergo TCR gene rearrangement.
Thymocytes undergo positive selection (in the cortex).
Thymocytes undergo negative selection (in the medulla); autoreactive thymocytes are removed.
Thymocytes become single-positive (SP) cells (either CD4+ or CD8+).

Dysregulation of Thymic Stroma

Thymic stromal disruptions can affect thymocyte selection, leading to autoreactive thymocytes escaping.
The thymic microenvironment is sensitive to damage from various stressors.
Thymic atrophy is a gradual decline in thymic function with aging.
Loss of thymocytes, collapse of the cortical-medullary junction, and an increase in adipocytes are hallmarks of atrophy.

MSCs in Other Tissues

MSCs have been isolated from other tissues but are not necessarily stem cells unless they show characteristics of self renewal and multipotency in vivo.
Stromal cells in various tissues provide structural support and chemical cues for immune cell regulation.
Ageing and hormones impact various organ systems (like the thymus) leading to reduced function and less diversity of T cells produced.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Test your knowledge on the effects of aging on mesenchymal stem cells (MSCs) and hematopoiesis. This quiz covers various aspects of how adipocytes impact these processes and the role of the thymus in T cell development. Dive into detailed questions about stem cell transplantation and the thymic microenvironment.