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Regenerative Medicine

Stem Cells: What They Are and How They Work

Stem cells can renew themselves and become specialized cells. Learn how scientists classify them, how they may work in the body, and what current research shows.

SANAA Team

5 min read

Updated on

A gloved hand holds a pipette over a multi-well cell culture plate in a laboratory.
Photo: National Center for Advancing Translational Sciences from Bethesda, MD, Public domain, Wikimedia Commons

Quick answer

What makes stem cells different from other cells?

Stem cells are cells that can renew themselves and differentiate into specialized cell types1. They are classified by origin and by how many cell types they can form, and they are studied for tissue repair, disease modeling, and drug screening12.

What types of stem cells are there?

Research reviews group stem cells into five broad categories: embryonic stem cells, very small embryonic-like stem cells, nuclear transfer stem cells, reprogrammed stem cells, and adult stem cells1. Among these, embryonic stem cells and induced pluripotent stem cells have shown great application promise in regenerative and transplant medicine, disease modeling, drug discovery screening, and human developmental biology1. Mesenchymal stem cells, a type of adult stem cell, are the subject of many registered clinical trials3.

Human embryonic stem cells are harvested from early-stage blastocysts about four to five days after fertilization or from later fetal tissues up to three months of gestational age, and they were the first stem cells used in research applications1. Induced pluripotent stem cells are derived from reprogrammed adult somatic cells using four transcription factors, a method first reported in 2006, and they can be expanded almost indefinitely and differentiated into most somatic cell types12. Mesenchymal stem cells, a type of adult stem cell, are multipotent and are found in various tissues, where they support tissue maintenance and repair34.

The five categories also differ in how they are obtained or generated, and these differences affect how scientists use them1. Very small embryonic-like stem cells were identified in 2006, and nuclear transfer stem cells were used to generate monkeys in China in 20181. In contrast, mesenchymal stem cells have a large number of registered clinical trials3.

Major stem cell categories described in the sources
TypeOrigin or sourceKey characteristicSource
Embryonic stem cellsEarly blastocyst (4–5 days postfertilization) or fetal tissueCan form tissues from all three germ layers; first used in research and still commonly used in clinical trials1
Induced pluripotent stem cellsReprogrammed adult somatic cells with four transcription factorsAlmost unlimited expansion; can differentiate into most somatic cell types12
Mesenchymal stem cellsBone marrow, umbilical cord, adipose tissue, and other tissuesMultipotent; help maintain tissue homeostasis and repair damaged tissue4

How do stem cells work in the body?

Stem cells support tissue maintenance and repair through two broad mechanisms: they can multiply to maintain their own numbers, and they can give rise to specialized cells that replace damaged or aged ones15. In addition, some adult stem cells, particularly mesenchymal stem cells, appear to work mainly by releasing signaling molecules that influence nearby cells34.

Mesenchymal stem cells are found in bone marrow, umbilical cord, adipose tissue, placenta, dental pulp, muscle, and other tissues, and they meet standard identity criteria that include plastic adherence, specific surface markers, and the ability to differentiate into bone, cartilage, and fat cells in vitro4. Researchers have observed that these cells can modulate the immune system and secrete growth factors, cytokines, chemokines, extracellular matrix components, and metabolic products; this paracrine activity is considered a major way they contribute to immune modulation, tissue remodeling, and cellular homeostasis34.

Stem cells reside in specialized microenvironments called niches, and their function depends on interactions with these niches5. During aging, stem cells in brain, muscle, blood, skin, and intestine show a decline in regenerative potential and differentiation ability, and defects in maintenance of quiescence, which is associated with loss of tissue integrity and health5.

What can stem cell research be used for in medicine?

Stem cell research is being studied for regenerative medicine, disease modeling, drug discovery and screening, and understanding human development12. In clinical trials, mesenchymal stem cells are being tested across a broad range of conditions, with registered trials mostly in traumatology, neurology, cardiology, and immunology3.

The clinical trial landscape for mesenchymal stem cells is broad, with many registered studies but fewer published results3. The following figures summarize the status of registered trials as of July 20203.

1,138trials

registered clinical trials involving mesenchymal stem cells as of July 2020

Source: 3

61.0%of trials

were in phase 2

Source: 3

30.8%of trials

were in phase 1

Source: 3

18trials

had published results by that date

Source: 3

Beyond mesenchymal stem cells, induced pluripotent stem cells are used in the laboratory to create models of human diseases, including neurological disorders, COVID-19, and cancer, and to screen drugs for therapeutic potential2. Researchers are also developing cell therapies from these cells2.

What are the challenges and future directions in stem cell research?

Although stem cell research has advanced rapidly, important challenges remain, especially for induced pluripotent stem cells, including controlling cell proliferation and differentiation1. Researchers are also investigating ways to maintain pluripotency and genomic stability in culture with feeder-free and xeno-free systems, and to use three-dimensional cell technologies and bioprinting1.

For mesenchymal stem cells, the field would benefit from more published trial results, since most registered studies had not yet reported outcomes as of the 2020 review3. A 2022 review emphasized that the therapeutic effects of these cells are largely due to their secreted factors, so understanding these secretions may be important for future applications4.

Another active area is stem cell aging: researchers are exploring interventions to rejuvenate old tissue stem cells and their niches, with the goal of countering age-related decline in tissue health5.

Frequently asked questions

Are all stem cells the same?

No. Stem cells differ in origin and potency13. Embryonic stem cells and induced pluripotent stem cells are pluripotent, while some adult stem cells, such as mesenchymal stem cells, are multipotent and more limited in what they can become13.

Where do mesenchymal stem cells come from?

Mesenchymal stem cells can be isolated from bone marrow, umbilical cord, adipose tissue, placenta, dental pulp, muscle, and other tissues; bone marrow has been the most common source in published clinical trials34.

Do stem cell treatments work?

Current evidence is encouraging but still developing3. A 2020 systematic review found that 18 published mesenchymal stem cell trials reported positive outcomes3.

What is an induced pluripotent stem cell?

It is an adult cell that has been reprogrammed in the laboratory to behave like an embryonic stem cell, using a small set of transcription factors first reported in 200612.

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