Lecture 14: Mesenchymal stem cells - Clinical trials and controversies

The process where MSCs don't permanently integrate into the injured tissue but still promote healing.

MSCs don't permanently become part of the injured tissue.

MSCs are trapped in the lungs during delivery, limiting their effectiveness in reaching the target tissue.

MSCs can influence immune cells, like T cells, to reduce inflammation.

MSCs can suppress the growth and activity of T cells and vice versa.

MSCs can reduce inflammation by affecting different immune cells.

MSCs can help in treating inflammatory conditions by calming down the immune response.

Apoptosis is a type of programmed cell death that happens silently without triggering an immune response. It involves proteolysis, a process where proteins are broken down, by caspases.

Apoptosis can occur through two main pathways: the intrinsic pathway, which is triggered from within the cell, and the extrinsic pathway, which is triggered by external signals.

MSCs (Mesenchymal stem cells) play a role in GVHD (Graft-versus-host disease) by inducing immunosuppression. This is because MSCs can undergo apoptosis and be engulfed by phagocytes, which then become immunosuppressive.

GVHD patients who respond well to MSC treatment have immune cells that effectively induce apoptosis in MSCs. This triggers the immunosuppressive response.

Phagocytes, which are immune cells that engulf dead cells, display immunosuppressive molecules like IDO, TGF-beta, PGE2, and IL-10 after engulfing apoptotic MSCs. This contributes to suppressing the immune response in GVHD.

MSCs may not permanently replace damaged tissues or stay in one place, but they release special molecules (like messengers) that can help control the immune system and reduce inflammation.

MSCs have a short lifespan and limited migration, meaning they don't survive long or spread far, yet they show positive effects on inflammation.

MSCs, when injected, tend to gather in the lungs. Allergic asthma, a lung disease, is a good model system to study how MSCs influence inflammation.

In allergic asthma, the allergen is taken up by a type of immune cell (dendritic cell). This cell presents the allergen to T cells, which then become TH2 cells.

TH2 cells produce special signaling molecules (cytokines) like IL-5, IL-4, and IL-13, which cause inflammation in the airways of the lungs.

IL-5 attracts eosinophils to the lungs.

IL-4 is crucial for B-cells to produce IgE antibodies, which are involved in allergic responses.

IL-13 triggers inflammation in the airways and makes goblet cells produce more mucus, contributing to the symptoms of asthma.

The combined effects of IL-5, IL-4, and IL-13 lead to the classic symptoms of an asthma attack.

Cells derived from bone marrow, umbilical cord, or adipose tissue that have the potential to differentiate into various cell types.

A standardized set of criteria used to identify and characterize MSCs, including their ability to adhere to plastic, form colonies, express specific markers, and differentiate into certain cell types.

A protein that plays a critical role in the recruitment of eosinophils, a type of white blood cell involved in allergic reactions.

A protein that contributes to airway hyperreactivity and airway function in asthma.

White blood cells that play a central role in allergic reactions, including asthma.

A model of asthma that uses ovalbumin (OVA), a common allergen, to induce symptoms in mice.

The process of exposing the body to an allergen to trigger an immune response, in this case, to OVA.

The introduction of an allergen into the airways, in this case, OVA.

Cells that are responsible for the secretion of mucus in the airways, often increased in number in individuals with asthma.

A reduction in the number of inflammatory cells, such as eosinophils, and goblet cells in the lungs of asthmatic mice after treatment with MSCs.

Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types, including bone, cartilage, and fat. MSCs are used in regenerative medicine to repair damaged tissues and organs.

MSCs are used in clinical trials to treat a variety of diseases, including asthma. The goal of these trials is to determine whether MSCs are safe and effective for treating these conditions. MSCs might improve asthma symptoms by reducing airway inflammation and improving lung function.

Airway hyperreactivity (AHR) is a common symptom of asthma, characterized by excessive bronchoconstriction (narrowing of the airways) in response to stimuli like allergens or exercise. This results in shortness of breath and wheezing.

Asthma is a chronic lung disease that inflames and narrows the airways. This inflammation makes the airways hypersensitive, resulting in symptoms like wheezing, shortness of breath, chest tightness, and coughing.

In asthma, excessive production of mucus can lead to increased resistance (Rl) in the airways, making it harder for air to flow through.

Dynamic compliance (Cdyn) is a measure of the elasticity of the lungs - how easily they can expand and contract. In asthma, lung elasticity is often reduced.

In asthma, MSCs are injected to the lungs, where they might exert a therapeutic effect by reducing airway inflammation, improving lung function, and reducing airway hyperreactivity.

The ability to induce MSC apoptosis (programmed cell death) can predict a patient's response to MSC treatment. If MSCs undergo apoptosis quickly, it might indicate a less effective treatment.

A study was conducted to track the fate of injected MSCs in asthmatic mice. The researchers used luciferase-expressing MSCs, which emit a glow in the presence of luciferin.

The study found that injected MSCs localized to the lungs, but they did not survive for long, disappearing within 2-3 days. This finding suggests that MSCs might not directly contribute to long-term tissue repair in asthma.