10.4: Regenerative Medicine

Biotech Focus

In 1956, several workers performing an experiment involving uranium fuel rods at the Vinča Nuclear Institute in Yugoslavia were exposed to high doses of radiation. Soon after, these men began experiencing the symptoms of acute radiation syndrome and were immediately transferred to the Curie Institute in Paris, where they underwent pioneering bone marrow transplants by the French oncologist Georges Mathé. All but one of the workers survived. This transplant represented the first use of stem cells as a medical treatment. Five years later, Canadian scientists Dr. James Till and Dr. Ernest McCulloch at the Ontario Cancer Institute in Toronto published their discovery of the hematopoietic stem cell (HSC), the stem cell that gives rise to all blood cells. Till and McCulloch injected bone marrow into irradiated mice and observed the formation of colonies in the spleen. Each colony originated from a single HSC and exhibited both self-renewal and differentiation - the two traits of a stem cell. Thanks to their pioneering work, the stem cell field, and related fields like tissue engineering, were made possible.

Introduction

Regenerative medicine is a branch of medicine that focuses on the repair, replacement, or regeneration of human cells, tissues, or organs in order to restore normal function. It takes advantage of the the body’s natural healing processes and often uses advanced technologies to accelerate or enhance those processes.

Key components of regenerative medicine include:

1. Stem Cell Technology: uses stem cells to develop into specific cell types and repair damaged tissues
2. Tissue Engineering: creates biological tissues in the lab using a combination of scaffolds, cells, and biologically active molecules
3. Biomaterials and scaffolds: uses synthetic or natural materials to support cell growth and tissue formation

Regenerative medicine has a wide range of applications, including the treatment of bone defects, damaged heart muscle, and spinal cord injuries, to potentially curing diabetes, Parkinson’s, and even organ failure without the need for transplantation. One of the most successful early applications of regenerative medicine was in the treatment of skin defects and burns. Early approaches involved the use of tissue grafts taken from the patient's own skin (i.e., autografts), cadavers (i.e., allografts), or animals like pigs (i.e., xenografts). However, each of these came with their own problems, like the secondary defect associated with an autograft or immune rejection associated with a xenograft. These problems led to the need for alternatives that regenerative medicine could provide. Today, physicians can use synthetic skin grafts made of bioengineered scaffolds, seeded with human epidermal and dermal cells, to treat non-healing wounds and partial-thickness burns (e.g., Apligraft, Stratagraft) or "cultured autografts" made of a patient's own keratinocytes grown in the laboratory (e.g. Epicell). With each advancement, regenerative medicine continues to expand its applications in medicine and offers hope for those living with disease, defect, or injury.

Learning Objectives

Regenerative medicine is a branch of medicine focused on repairing, replacing, or regenerating human cells, tissues, or organs to restore normal function. At the end of this page, you will be able to:

• Define key terms associated with regenerative medicine, like stem cell, differentiation, and potency
• List and explain the three key components of regenerative medicine
• List and explain the three major types of potency associated with a stem cell
• Compare and contrast the three major categories of stem cells
• Describe some commonly used stem cells
• List the components used in tissue engineering
• Explain the different types materials used in making a scaffold
• Explain some methods commonly used to make a scaffold
• Explain what a bioactive molecule is and list some types used in tissue engineering

Stem Cell Technology

A stem cell is an undifferentiated (i.e., unspecialized) cell that can differentiate (i.e., specialize) into a specific cell type like a muscle cell or a blood cell (Figure \(\PageIndex{1}\)). Stem cells also exhibit the property of self-renewal, in that they divide to produce a daughter cell that continues on as a stem cell and another daughter cell that is destined to differentiate. Differentiation is the biological process in which a stem cell develops into a specialized cell type with a distinct structure and function. This differentiation is critical for the determination of a cell's lineage, the developmental history of a cell as it divides and differentiates into other cell types. In order for a lineage to be determined, stem cells "choose" a cell fate that directs the type of cell they will become. The tissue continues its development and the lineage is set. For example, a stem cell population whose cell fate is restricted to the osteogenic lineage will differentiate into osteoblasts, followed by direct bone tissue formation.

Figure \(\PageIndex{1}\): Stem cell differentiation. The stem cell differentiates in specific cell types such as epithelial, immune, sex, muscle, fat, bone, blood, and nervous cells (i.e., neurons) (Stem Cell by Haileyfournier, CC BY-SA 4.0)

Differentiation of a stem cell is directed by the expression of specific genes that restrict the stem cell's potency and result in its morphological and metabolic transition to a new cell type. Even today, researchers continue to study the cellular and molecular mechanisms that underlie stem cell differentiation in the hopes of more effectively using stem cells in regenerative medicine. The ability of a stem cell to differentiate is determined by their potency. Stem cell potency refers to a stem cell's ability to differentiate into different types of cells. Most stem cells can be described as having one of three types of potency (Figure \(\PageIndex{2}\)):

• Totipotent: stem cells can develop into any cell type in the body and the extraembryonic tissues.
  • e.g., early-stage embryonic stem cells (i.e. up to the 16-cell stage)
• Pluripotent: stem cells can become any cell type in the body (i.e., all three germ layers: ectoderm, mesoderm, endoderm), but not extraembryonic tissues
  • e.g., embryonic stem cells and induced pluripotent stem cells
  • Widely used in regenerative medicine
• Multipotent: stem cells have limited potency and can differentiate into a limited number of cell types within a germ lineage (e.g., mesoderm)
  • e.g., hematopoietic stem cell (HSC), mesenchymal stem cell (MSC), and the adipose-derived stem cell (ASC)
  • Limited use in regenerative medicine that is restricted to the corresponding cell lineage - e.g. HSCs for generation of blood cells; MSCs for the generation of mesenchymal tissues (i.e., fat, bone, cartilage, muscle)

Figure \(\PageIndex{2}\): Stem cells have specific potency. The 16-cell embryo is made of cells called totipotent stem cells. Over time the embryo develops into a blastocyst. The inner cell mass of the blastocyst is a population of pluripotent stem cells. These stem cells develop into the mesoderm, endoderm, and ectoderm germ lines. Germ line development results in the formation of several kinds of multipotent stem cells like mesenchymal stem cells (MSCs) that can develop into bone, fat, and muscle cells, hematopoietic stem cells (HSCs) that form the blood cells, and neural stem cells that develop into neurons and the glial cells of the nervous system. (Stem Cells by Patricia Zuk, CC BY 4.0; figure created in BioRender. Zuk, P. 2025)

Embryonic development results in the loss of stem cell potency as the totipotent stem cell population of the 16-cell zygote is replaced with the pluripotent stem cells of the inner cell mass. These pluripotent stem cells will become distributed throughout the embryo and will restrict their potency to become the various populations of multipotent stem cells. The loss potency during embryonic development is directed, in part, by environmental signals found in the developing tissue. In humans, the majority of tissues contain multipotent stem cells that direct tissue repair following damage.

With each passing year, there seems to be a new population of stem cells being discovered and used in regenerative medicine. However, there are only three recognized categories of stem cells: embryonic, fetal, and adult. Each stem cell population is classified into one of these three categories. Embryonic stem cells (ES) cells, fetal stem cells, and adult stem cells differ in their origin, potency, and applications (Table \(\PageIndex{1}\)).

Table \(\PageIndex{1}\): Embryonic vs. Adult Stem Cells

Feature	Embryonic Stem Cells (ES cells)	Fetal Stem Cells	Adult Stem Cells
Origin	isolated from the inner cell mass of a blastomere (animal) or blastocyst (human)	isolated from fetal tissues after 8 weeks of gestation	isolated from tissues such as bone marrow, adipose tissue, and skin
Potency	totipotent or pluripotent	mostly multipotent	mostly multipotent
Self-renewal ability	high	lower in comparison to ES cells	relatively low; self-renewal depends on the type of adult stem cell
Potential for tumor formation	high - can form teratomas (tumors) due to uncontrolled growth	lower in comparison to ES cells	low
Potential for immune rejection	high - ES cells may be rejected if not genetically matched to the recipient	lower in comparison to ES cells; similar to adult stem cells	low; often isolated from autologous tissues
Applications	regenerative medicine - organ regeneration and tissue repair (e.g. Parkinson’s, diabetes, spinal cord injuries) disease modeling drug testing	regenerative medicine - organ regeneration and tissue repair (e.g. Parkinson’s, diabetes, spinal cord injuries) disease modeling drug testing	regenerative medicine - organ regeneration and tissue repair (e.g. Parkinson’s, diabetes, spinal cord injuries) disease modeling drug testing
Ethical considerations	high - use of human ES cells requires destruction of human blastocysts	high - used of fetal stem cells requires the use of fetal tissues	low - human adult stem cells are isolated from consenting donors

In practice, a stem cell is identified by its ability to repair or regenerate tissue. Since the discovery of hematopoietic stem cells (HSCs) in the 1960s, stem cells have been utilized in a wide variety of regenerative medicine applications, such as:

1. Hematopoietic Stem Cells (HSCs): for the treatment of blood cancers (like leukemia, lymphoma), aplastic anemia, and some immune disorders.
   • uses several sources of HSCs, including bone marrow, peripheral blood, or umbilical cord blood
   • the most widely used and established stem cell therapy worldwide
2. Epidermal stem cells: for the treatment of large-area burns using autologous skin grafts
   • use of autologous epidermal stem cells donated by the patient
   • products like Epicel (cultured epidermal autografts) are FDA-approved
3. Mesodermally-derived stem cells: for the regeneration of a variety of mesodermally-derived tissues
   • use of autologous stem cells from bone marrow (i.e., MSCs) or adipose tissue (e.g., ASCs)
   • regeneration of cartilage in patients with joint injuries or early osteoarthritis (e.g., Carticel)
   • treatment of spinal cord injuries (e.g., Stemirac)
   • treatment of graft vs. host disease in young children( e.g., Ryanocil)
4. Adipose-derived Stem Cells (ASCs): for the repair of complex perianal fistulas that do not respond to conventional treatments
   • use of allogeneic ASCs
   • approved in the EU (e.g., Alofisel),with strong efficacy and safety data

The majority of regenerative medicine applications using stem cells utilize adult stem cells due to their ease of isolation and lack of ethical concerns. This is in direct contrast to the use of ES cells. The ethical considerations that continue to surround the isolation and use of human ES cells has led researchers to develop the induced Pluripotent Stem Cell (iPSC). iPSCs have been artificially reprogrammed to behave like ES cells through the introduction of four specific genes (Oct4, Sox2, Klf4, c-myc) into fully differentiated cells, such as skin or blood cells. This genetic reprogramming appears to return the somatic cell to a more pluripotent state. Because of their high level of potency and their derivation from adult cells, iPSCs have been suggested as a replacement for ES cells. As such, iPSCs are used in disease modeling, drug testing, personalized medicine and regenerative medicine. However, their use in personalized and regenerative medicine has not been as widely explored as ES cells and adult stem cells. Furthermore, the significant degree of genetic changes required to create an iPSC may eliminate them from many applications in regenerative medicine. Despite this, stem cell therapy continues to be promising due to their potential therapeutic application in replacing defective or damaged cells resulting from a variety of disorders and injuries, such as Parkinson disease, heart disease, and diabetes.

Tissue Engineering

Tissue engineering is a multidisciplinary field that combines biology, engineering, and medicine in order to focus on the development of biological substitutes to restore, maintain, or improve tissue function. Tissue engineering combines components:

1. Cells: the living units responsible for forming functional tissue
   • can be precursor cells or stem cells
   • can be either autologous (harvested from the patient in order to minimize immune rejection) or allogeneic (donated cells)
2. Biological scaffolds: 3D structures that provide a biocompatible, physical structure for the attachment, proliferation, and differentiation of cells
   • made of natural, synthetic, or composite materials
3. Bioactive molecules: growth factors and other signaling cues that guide cell behavior and tissue development within the scaffold

In the typical tissue engineering approach, these three components interact with one another inside a bioreactor, a controlled environment designed to mimic physiological conditions and support tissue formation.

By integrating cells, scaffolds, and signaling molecules, tissue engineering aims to repair or regenerate damaged tissues and organs. Examples of tissues generated through tissue engineering include:

• Skin: bioengineered skin substitutes consisting of keratinocytes and fibroblasts layered on a scaffold (e.g., Apligraf, Dermagraft) used for chronic wounds and burns
• Cartilage: autologous chondrocyte implantation (ACI) or stem-cell seeded scaffolds to repair joint damage
• Bone: hydroxyapatite or tricalcium phosphate scaffolds combined with pre-osteoblast precursors of adult stem cells
• Blood vessels: vascular grafts engineered from endothelial and smooth muscle cells for the replacement of damaged vessels; e.g. coronary bypass vessels

Tissue engineering is also being used in the generation of whole organs such as liver, kidney, and heart tissues. Miniature versions of organs, called organoids, are being developed in lab settings, although clinical applications remain limited.

The use of tissue engineering principles in tissue repair is promising. However, there are several obstacles to overcome. Vascularization is one of them. Supplying nutrients to thick tissue layers remains a significant challenge. While autologous cells are often used to decrease the chances of an immune response, such as response can occur due to scaffold materials or altered cell behavior. Regulatory hurdles must be cleared in order to ensure the safety and efficacy of engineered tissues. These hurdles can delay the transition of the clinic. Lastly, manufacturing scale-up remains an issue as generating tissues at a large scale both reproducibly and cost-effectively is a significant challenge.

Biomaterials and Bioscaffolds

A biomaterial is any natural or synthetic material that is designed to interact with a biological system (e.g. cells, tissues) for a medical purpose, such as the therapeutic delivery of drugs or cells for tissue repair. Biomaterials must be biocompatible and not provoke an immune reaction. They should bioactive to promote the attachment, proliferation, and/or the differentiation of cells. They should match the mechanical demands of the target tissue (e.g, load bearing vs. non-load bearing). Finally, many biomaterials are designed to be biodegradable so that they degrade safely in the body.

A bioscaffold (i.e., scaffold) is a three-dimensional structure made of a biomaterial. The composition of a bioscaffold is chosen to be compatible with the cells being used and the tissue being regenerated. The scaffold must promote the viability of the cells seeded onto the scaffold. In addition, it should also integrate into the surrounding tissue so that the tissue being regenerated is compatible. Scaffold compositions used in tissue engineering are natural polymers, synthetic polymers, or composite materials that combine both natural and synthetic biomaterials. Each of these compositions have advantages and disadvantages that must be considered before being used in a tissue engineering application. For example, synthetic polymers have the advantages of consistent composition, higher mechanical strength, and controlled degradation in situ. However, their degradation may create toxic materials. The composition and design of the scaffold ultimately used must consider porosity, mechanical strength, biodegradability, and surface chemistry so as to support cellular function and integration.

Natural polymers include collagen, fibrin, alginate, and chitosan (Table \(\PageIndex{2}\)). These materials have the advantages of being bioactive and biocompatible. However, they can be variable in composition and have lower mechanical strength.

Table \(\PageIndex{2}\): Natural Scaffold Materials

Material	Source	Tissue Engineering Application	Key Features
Collagen	animal connective tissues	skin, bone, cartilage	biodegradable, cell-friendly
Fibrin	blood plasma	wound healing, cardiovascular patches	promotes angiogenesis
Alginate	brown seaweed	soft tissue engineering	mild gelation, controlled stiffness
Chitosan	crustacean shells	cartilage, wound healing	antimicrobial, highly biodegradable
Hyaluronic acid	connective tissue matrix	cartilage repair, cell delivery system	hydrating, similar to cartilage matrix

Common synthetic materials used in biological scaffolds include polylactic acid (PLA) and polyglycolic acid (PGA), in addition to calcium phosphate-based scaffolds like hydroxyapatite (Figure \(\PageIndex{3}\)) and tricalcium phosphate (Table \(\PageIndex{3}\)).

Table: \(\PageIndex{3}\): Synthetic Scaffold Materials

Material	Type	Tissue Engineering Applications	Key Features
PLA (Polylactic acid)	thermoplastic polyester	bone, skin, guidance of nerves	biodegradable, FDA-approved for load-bearing tissues like bone
PGA (Polyglycolic acid)	synthetic polymer	cartilage, nerve, skin	fast degradation
PLGA (Poly(lactic-co-glycolic acid))	co-polymer	bioactive factor delivery, tissue patches	controlled degradation
PCL (Polycaprolactone)	synthetic polymer	ligaments and tendons, cartilage, vascular tissue	slow degradation, flexible
PEG (Polyethylene glycol)	hydrophilic polymer	cartilage, nerve, vascular tissue, cornea	mimics soft tissue
Hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂)	calcium phosphate-based material	bone	slow degradation, good for load-bearing tissues, mimics ECM of bone
Tricalcium phosphate (TCP)	calcium phosphate-based material	bone	fast degradation

Figure \(\PageIndex{3}\): Hydroxyapatite crystals. This electron micrograph shows an extensive network of hydroxyapatite crystals that closely mimics the matrix of bone tissue. (Crystals of Hydroxylapatite by Nabilah, CC BY-SA 4.0)

Composite scaffolds combine natural and synthetic materials for optimized performance, balancing biocompatibility and mechanical integrity. Examples include collagen-PLGA and hydroxyapatite–PCL for bone and cartilage repair.

Bioscaffolds can be produced using several methods including:

1. Solvent Casting and Particulate Leaching (SCPL): used for PLGA, PGA, PCL, hydroxyapatite, tricalcium phosphate scaffolds
   • Production method: a polymer is dissolved in a solvent and mixed with salt or sugar particles (i.e. porogens)
     • the mixture is cast into a mold
     • the solvent is evaporated and immersed in water to dissolve the porogen
   • Pros: simple and inexpensive to make; pore sizes controlled by porogen; good for cell infiltration, can be coated with natural materials like collagen
   • Cons: limited control over pore interconnectivity; residual solvent or porogen may be toxic if not fully removed
   • Used for: bone and cartilage
2. Electrospinning: used for PLA or PCL synthetic scaffolds and numerous natural materials (e.g., collagen)
   • Production method: a polymer solution is fed through a needle with a high-voltage electric field to create fine fibers that collect on a grounded surface
   • Pros: excellent surface area for cell attachment; mimics native ECM structure well
   • Cons: typically made as a 2D or thin 3D scaffold; poor cell infiltration unless the scaffold is layered
   • Used for: skin, nerve, vascular, and soft tissue
3. 3D printing: most natural and synthetic scaffold materials
   • Production method: layer-by-layer printing of scaffold material using a 3D printer and its software
   • Pros: Can be customized to print a variety of scaffold shapes
   • Cons: Cost; requires a 3D printer and software
   • Used for: vascular grafts, cartilage, bone scaffolds

Concept in Action

Electrospinning Technology

Bioactive Molecules

A bioactive molecule is any compound that affects tissues or cells by producing a specific physiological response. Common bioactive molecules include growth factors, peptides, and hormones. In order to be a bioactive molecule, the compound must bind to receptors on the cell surface and trigger signaling pathways that influence cell fate and behavior (e.g., migration, growth, differentiation). In tissue engineering, bioactive molecules promote the adhesion, proliferation, and differentiation of cells (including stem cells), promote angiogenesis, nerve regeneration and remodeling of tissues, and modulate the immune response to implants. Table: \(\PageIndex{4}\) below outlines some common bioactive molecules used in tissue engineering.

Table: \(\PageIndex{4}\): Bioactive Molecules

Type of Bioactive Molecule	Function	Example
Growth Factors	Stimulate cell growth, migration, or differentiation	BMPs, VEGF, FGF, EGF, TGF-β
Cytokines	Modulate immune response or inflammation	IL-1, IL-6, TNF-α, IFN-γ
Peptides	Mimic protein domains for cell signaling	RGD peptide (cell adhesion), IKVAV
Hormones	Regulate cell metabolism and function	Insulin, estrogen, parathyroid hormone
Extracellular Matrix (ECM) Proteins	Provide structural and signaling support	Collagen, fibronectin, laminin
Small Molecules	Modulate cell signaling	Dexamethasone, retinoic acid, valproate
Antibodies	Target or block specific receptors or proteins on cells	Anti-VEGF, anti-TNF antibodies
Nucleic Acids	Regulate gene expression	siRNA, miRNA

Bioactive molecules used in tissue engineering can be incorporated into scaffolds for the slow release of the molecule, attached to the surface of a biomaterial to affect surrounding cells, and encapsulated in microspheres/nanoparticles. Today, "smart biomaterials" are being designed to release bioactive factors in response to stimuli like pH, temperature, or electric fields.

Emerging Breakthroughs

Today, there are several promising approaches being proposed for tissue engineering. One such approach is called "bioprinting". Bioprinting is based on 3D printing technology but uses "bioinks" which are combinations of biomaterials, living cells, and bioactive materials. Like 3D printing, bioprinted scaffolds are layer by layer in a 3D printer. However, these printers have been modified to use bioinks. Bioprinting is highly precise and can be customized to create complex structures seeded with living cells and embedded with bioactive compounds. However, bioprinting remains expensive, as the bioprinter is more advanced then the standard 3D printer used in labs today. In addition, the bioinks must finely tuned to balance printability with biocompatibility. Bioprinting is currently being used for the creation of soft tissue scaffolds like vascular grafts and tubes. Researchers are using bioprinting to create miniature versions of organs (i.e., organoids) in order to advance bioprinting to the point where life-sized organs can be made.

Concept in Action

Bioprinting Human Tissues

Another approach is the use of decellularized tissues (i.e. decellularized ECM or dECM). Tissue-specific scaffolds can be created by removing cells from a donor tissue while preserving the overall 3D structure of the tissue and its matrix proteins. Examples include the experimental use of decellularized trachea, tendons, ligaments, and heart matrix, in addition to the commercial use of decellularized skin grafts (e.g., Alloderm and DermACELL) and small intestine submucosa (e.g., SurgiSIS and Oasis). Decellularized tissues have the advantage of being perfectly suited to the tissue they are repairing. However, the possibility of an immune reaction upon implantation cannot be completely discounted.

Concept in Action

The Science of Decellularization

The progress made in tissue engineering over the last two decades has been astounding. Of course, obstacles still remain. Organ regeneration is complicated by the sheer size and thickness of the organ. As such, the formation of a functional vasculature and innervation remains elusive in large tissue and organ constructs. Scaling up manufacturing without compromising the bioactivity of the engineered construct is challenging. Ensuring long-term integration and safety in humans and navigating the ethical and regulatory hurdles, especially in organ engineering, will need be to addressed. Despite these challenges, the future remains bright for tissue engineering.

Key Concepts

Regenerative medicine is a branch of medicine that focuses on the repair, replacement, or regeneration of human cells, tissues, or organs in order to restore normal function.

Some important concepts to remember are:

• regenerative medicine uses tissue engineering techniques to repair or regenerate tissues
• tissue engineering uses cells, biomaterials, and bioactive molecules to regenerate and repair tissues
• the cells used in tissue engineering can be precursor cells or stem cells
• stem cells are unspecialized cells that can divide and differentiate
• stem cells can be totipotent, pluripotent, or multipotent
• each stem cell population has its own unique set of advantages and disadvantages
• biomaterials are any natural or synthetic materials that are designed to interact with a biological system
• biomaterials include scaffolds
• scaffolds can be made of natural or synthetic biomaterials or a combination of both
• scaffolds can be made through techniques like particulate leaching, electrospinning, or 3D printing
• bioactive molecules are compounds that affect tissues or cells by producing a physiological response
• bioactive molecules include growth factors, peptides, hormones, or matrix proteins
• emerging technologies in tissue engineering include the use of decellularized matrices or bioprinting
• bioprinting uses "bioinks" that are a combination of living cells, bioactive molecules, and biomaterials

Glossary

Bioactive molecule - a substance that interacts with living cells or tissues to influence their behavior, such as promoting growth, differentiation, or healing; examples include growth factors, cytokines, or peptides

Biocompatible - a material or substance that can be safely introduced into the body to supports normal cellular function without causing an immune response or toxicity

Biodegradable - a material that can be broken down naturally by biological processes in the body into harmless byproducts over time

Bioink - a printable biomaterial, containing cells and biocompatible hydrogels, that is used in 3D printing to fabricate tissue-like structures layer-by-layer

Biomaterial - any natural or synthetic material used to interact with or replace a biological tissue

Bioprinting - a form of 3D printing that uses bioinks to create complex biological structures, such as tissues or organs

Bioscaffold - a 3D framework used in tissue engineering that is made of biomaterials designed to support cell attachment, proliferation, and differentiation

Decellularized - a term that describes a tissue or organ that has had all cellular material removed, leaving behind the extracellular matrix to be used as a scaffold

Differentiation - a biological process by which a less specialized stem cell becomes a more specialized cell type

Extracellular matrix (ECM) - a complex network of proteins and molecules surrounding cells in tissues; provides structural support and biochemical signals for cell behavior

Lineage - the development "history" of a cell

Multipotent - a term that describes stem cells that can differentiate into multiple, but limited, cell types within a specific cell lineage; e.g., mesenchymal stem cells into bone, fat, or cartilage

Organoid - a miniature, simplified version of an organ grown in vitro from stem cells, that mimics key structural and functional properties of the real organ

Pluripotent - a term that describes stem cells that can give rise to all cell types in the body; found in the inner cell mass of the embryo

Polymer - a large molecule made up of repeating units called monomers

Potency - the measure of a stem cell's ability to differentiate into different cell types; ranges from totipotent to unipotent

Precursor cell - a cell that is restricted in its lineage to only one type of cell; e.g., a pre-osteoblast precursor becomes an osteoblast

Regenerative medicine - a field of medicine that aims to restore or replace damaged tissues and organs using techniques like stem cell therapy, tissue engineering, and gene editing

Scaffold - a natural or synthetic 3D structure that provides physical support for cells used in tissue engineering; also called a bioscaffold

Stem cell - an undifferentiated cell capable of self-renewal and differentiation depending on its potency

Totipotent - a term that describes stem cells that are able to give rise to all cell types of the body and the extra-embryonic tissues; found in early stage embryos (i.e. up to 16-cell)

Unipotent - a term that describes a cell that has the capacity to differentiate into only one specific cell type, but they still retain the ability to self-renew