What Is the Difference Between Pluripotent and Multipotent Stem Cells?

A stem cell is defined by two capabilities: self-renewal (dividing to produce more copies of itself) and differentiation (transforming into specialized cell types, such as nerve, muscle, or blood cells). The range of cell types a stem cell can become is called its “potency.” Understanding these levels of potency is the basis for classifying stem cells and determining their utility in biological research and medicine.

Mapping the Full Scale of Cell Potency

Stem cell potency exists along a spectrum, ranging from the most flexible to the most restricted developmental potential. At the highest end are totipotent cells, such as the fertilized egg and early division cells. These cells possess the total potential to form every cell type in the developing organism, including extraembryonic tissues like the placenta and umbilical cord.

Pluripotent cells represent the next level of potential, capable of forming almost all cell types that make up the body. However, they cannot form the extraembryonic structures necessary for a whole organism, which distinguishes them from totipotent cells. The scale continues to multipotent cells, which have a narrower scope, restricted to forming only a limited set of specialized cells, usually within a specific tissue lineage.

The most restricted cells are unipotent cells, which can only produce one specialized cell type, though they still retain the self-renewal ability of a stem cell. For example, a unipotent stem cell might only produce skin cells. This hierarchical organization establishes the framework for understanding the biological limitations and therapeutic promise of pluripotent and multipotent cells.

Pluripotency Explained: Creating Any Cell in the Body

Pluripotent cells are defined by their ability to generate any cell derived from the three embryonic germ layers: the ectoderm, mesoderm, and endoderm. The ectoderm forms the nervous system and skin, the mesoderm forms tissues like muscle, bone, blood, and the heart, and the endoderm develops into the linings of the digestive and respiratory tracts, liver, and pancreas. The potential to form all three foundational cell lineages makes pluripotent cells valuable for research.

The two main sources of pluripotent cells are Embryonic Stem Cells (ESCs) and Induced Pluripotent Stem Cells (iPSCs). ESCs are naturally derived from the inner cell mass of the blastocyst, an early-stage embryo. These cells are inherently pluripotent and can be maintained indefinitely in an undifferentiated state in a laboratory setting.

A significant breakthrough came with the creation of iPSCs, which are adult somatic cells (such as skin or blood cells) genetically reprogrammed back into a pluripotent state. This process involves introducing a specific set of transcription factors, including Oct4, Sox2, Klf4, and c-Myc, which effectively “reset” the adult cell’s identity. Generating iPSCs from a patient’s own cells bypasses the need for embryos and provides a source of genetically matched, pluripotent cells.

Multipotency Explained: Restricted to a Specific Lineage

Multipotent stem cells are characterized by a significant restriction in their differentiation potential compared to pluripotent cells. They can only differentiate into a limited range of cell types closely related to the tissue in which they originate. This means a multipotent cell from one system, such as the circulatory system, cannot produce cells belonging to a different system, like the nervous system.

A prime example of multipotency is the Hematopoietic Stem Cell (HSC), which resides primarily in the bone marrow. HSCs are responsible for producing all distinct blood cell types, including red blood cells, white blood cells, and platelets. Their potential is broad within the blood lineage but strictly confined to that system; they cannot form bone or nerve tissue.

Another common example is the Mesenchymal Stem Cell (MSC), found in various adult tissues, notably bone marrow and adipose (fat) tissue. MSCs differentiate into a limited number of tissue-specific cells, predominantly those of the connective tissue lineage, such as osteocytes (bone cells), chondrocytes (cartilage cells), and adipocytes (fat cells). This restriction highlights their role in maintaining and repairing the specific tissues in which they reside.

Current Research Focus and Therapeutic Use

The differences in potency directly dictate the current applications of these two cell types in medicine and research. Multipotent stem cells are already utilized in established clinical procedures due to their specialization and ease of access from adult tissues. The most successful therapy involves the transplantation of Hematopoietic Stem Cells (HSCs) to treat blood cancers, such as leukemia, and certain immune disorders.

Pluripotent cells, particularly iPSCs, are primarily focused on research and the development of future regenerative therapies. Their broad potential makes them ideal for creating patient-specific disease models in a petri dish, allowing scientists to screen for new drug treatments using cells that carry a patient’s exact genetic makeup. Pluripotent cells are also used to generate complex, new tissues or organs, such as functional heart muscle or pancreatic cells, for transplantation.

The clinical translation of pluripotent cells is more complex due to the challenge of precisely controlling their differentiation and the risk of generating teratomas—tumors containing tissues from all three germ layers—if undifferentiated cells remain. While multipotent cells are currently used for tissue-specific repair and blood replenishment, pluripotent cells are being harnessed to model disease and eventually generate replacements for virtually any damaged tissue.