What Is Regenerative Medicine? How Stem Cell-Based Treatment Works

What is regenerative medicine?#

Regenerative medicine is medicine that aims to repair and regenerate cells, tissues, and organs damaged by illness or injury.

The technologies used in regenerative medicine are not limited to stem cells. For example, stem-cell and cell therapies, cells produced from iPS cells, tissue engineering, biomaterials, gene therapy, and tissues made from cells are all being studied.

In other words, regenerative medicine does not equal stem-cell therapy. Stem-cell therapy is one of its methods.

Why are stem cells used in regenerative medicine?#

Stem cells have two key characteristics.

1. Self-renewal: the ability to produce more cells with the same properties.

2. Differentiation: the ability to change into other cell types under certain conditions.

Using these properties, it may be possible to replace cells and tissues lost to disease or injury, or to create an environment that supports tissue repair.

The basic flow of stem-cell-based regenerative medicine#

Treatments using stem cells vary greatly depending on the cell type and method. As a general image of cell therapy, the flow is as follows.

STEP 1 Collect cells — When using the patient's own cells, cells may be collected from bone marrow, fat tissue, or similar sources. Some treatments use donor-derived cells instead.

STEP 2 Process and culture cells — Collected cells may be used as they are, or cultured and processed according to the purpose. The required steps differ by cell type and treatment.

STEP 3 Administer to the patient — Cells are given by a method suited to the treatment goal: intravenously into blood vessels, directly into the damaged site, or transplanted as tissue.

What do stem cells do once inside the body?#

This is an especially important point for understanding stem-cell therapy. You might picture it as 'the administered stem cells transform into the damaged cells and rebuild the tissue.'

However, at least for mesenchymal stem/stromal cells (MSCs), research has shown that this alone cannot explain their effects. Current research considers several broad mechanisms.

1. Moving to damaged tissue — Some administered MSCs show 'homing,' gathering at sites of inflammation or tissue damage, thought to involve interactions between MSCs and signals released from the damaged area. Not all administered cells gather at the target tissue, however, and their distribution and survival in the body differ by administration method and cell type.

2. Releasing growth factors and cytokines — A particularly noted feature of MSCs is that they secrete various substances. MSCs release growth factors, cytokines, chemokines, and other intercellular signaling molecules. These substances act on surrounding cells and may affect cell survival, proliferation, blood-vessel formation, and inflammatory responses. This signaling to nearby cells is called the 'paracrine effect.'

3. Regulating inflammation and immune responses — MSCs are also being studied for effects that regulate immune-cell activity. When tissue is damaged, inflammation occurs. Inflammation is necessary for repair, but excessive, prolonged inflammation can damage tissue. MSCs may modulate inflammation by influencing immune cells through various signals. So in MSC-based regenerative medicine, 'creating an environment in which tissue repairs more easily' is as important a concept as 'increasing cells.'

4. Possibly promoting angiogenesis — Repairing damaged tissue also requires blood to supply oxygen and nutrients. Some factors secreted by MSCs have been reported to be involved in angiogenesis, so MSC treatments are also being studied for supporting blood flow and vessel formation in damaged tissue.

5. Possibly replacing damaged cells directly — Because stem cells can differentiate, one idea is that administered cells differentiate into target cells and replace lost ones. This is especially important in regenerative approaches that produce and transplant specific cells — for example, research transplanting cells made from iPS cells into patients. For MSCs, however, the central effect is not necessarily that administered cells engraft in large numbers and build new tissue; studies have shown that MSC engraftment rates are low and that direct cell replacement alone cannot fully explain the benefits.

The mechanism in short#

For mesenchymal stem cells in particular, multiple mechanisms are thought to work together: 1. interaction with the damaged site, 2. secretion of growth factors and cytokines, 3. regulation of inflammation and immune responses, 4. effects such as angiogenesis, and 5. differentiation into some cells.

Going deeper#

Once the basics click, the next question is whether a given stem cell is already an approved treatment or still a research subject — the same word can mean very different things.

Reading the Evidence and Safety categories next, and checking unfamiliar terms in the glossary, will sharpen how you read future material.