CTERM

Understanding the Research

Regenerative medicine is the process of using cells, biomaterials, and molecules to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects. This field holds the promise of regenerating damaged tissues and organs in the body by stimulating previously irreparable organs to heal themselves.

Regenerative medicine also empowers scientists to grow tissues and organs in the laboratory and safely implant them when the body cannot heal itself. Importantly, regenerative medicine has the potential to solve the problem of the shortage of organs available through donation compared to the number of patients that require life-saving organ transplantation. Since stem cells are cells with have the ability to grow and differentiate into more than 200 cell types, they have been widely used for tissue engineering and regenerative medicine.

Stem cells have the unique ability to self-renew and differentiate down a number of developmental lineages. Adult stem cells, in particular, which are the focus of the Center, are multipotent, patient-derived stem cells that, in addition to self-renewal and differentiation potential, also possess immunomodulatory properties that allow for simpler cell-based therapies to have a significant impact. Clinically relevant adult stem cells can be isolated after the birth of a baby from both umbilical cord blood and tissue as well as from the placenta.

Additionally, adult stem cells can be harvested from a patient’s own bone marrow or adipose tissue. All of these cells are of the mesenchymal or hematopoietic cell lineage and so naturally give rise to bone, cartilage, muscle, fat, blood, and some cells of the immune system. The replicative potential of these cells in the lab allows for expansion. The differentiation potential of these cells allows for directing cell fate and generation of replacement cells. Finally, tThe immunomodulatory properties of these cells allows for direct cellular injection to suppress inflammation and aid in natural wound and injury repair. The full potential of these cells is still being discovered, but the current protocols already offer therapeutic value, while continued research is critical to enhance the clinical relevance and accessibility of these treatments.

The natural ability of stem cells to self-renew and differentiate is enhanced by a highly specific, 3D microenvironment that surrounds them in native tissue. These niches provide the structural, biochemical, mechanical, and stimulatory cues crucial for the appropriate functionality of the stem cells during homeostasis and in response to physiological changes. A significant challenge for the use of all stem cells in tissue engineering and regenerative medicine lies in providing the proper environmental cues to regulate the balance between self-renewal and differentiation. High-throughput biomanufacturing and regenerative medicine applications require an understanding of how the niche controls stem cell function and developing technology that can synthetically mimic those environments in 3D.

Regenerative medicine and tissue engineering seek to address this need by creating biocompatible materials that facilitate the generation of clinically relevant tissues for therapeutic applications. The field, termed “tissue engineering,” is a multidisciplinary field that focuses on the development of intelligent, biocompatible materials that can serve as a “scaffold” for repair and/or replacement of damaged tissue. Tissue engineering has the potential to improve the health and quality of life for millions of people by restoring and maintaining tissue and organ function. Scaffolds composed of materials with optimal chemical and physical properties, adequate cell sources, and appropriate biochemical or biophysical cues are the backbone of research in the tissue engineering field. For these constructs to be successful they need to be analogous to the natural environment of the extracellular matrix (ECM) of the niche in which they will be implanted. Current approaches in tissue engineering and regenerative medicine use a variety of cell types to determine the most efficient and effective therapy option.

In all cases, the success depends not only on the cell, but the chemical and physical cues that direct the cells toward a particular cell fate. The main challenge is how to fully recreate the stem cell’s native extracellular environment, which supports maintenance of pluripotency and controls differentiation. This is due in part due to a lack of understanding of spatial and temporal mechanisms that specifically govern stem cell fate determination within their environments. The allure of regenerative medicine promises to redefine medical treatment, putting stem cells and biocompatible materials center stage in this revolution. Many breakthroughs have been reported and hailed in scientific journals and the media over the years. But despite these successes and the fact that scientists around the world are furiously working on new therapies, regenerative medicine treatments have not entered mainstream medical practice in most areas of medicine.

Helpful terms

Tissue engineering

Tissue engineering evolved from the field of biomaterials development and refers to the practice of combining scaffolds, cells, and biologically active molecules into functional tissues. The goal of tissue engineering is to assemble functional constructs that restore, maintain, or improve damaged tissues or whole organs.

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Regenerative medicine

Regenerative medicine is a broad field that includes tissue engineering but also incorporates research on self-healing – where the body uses its own systems, sometimes with help foreign biological material to recreate cells and rebuild tissues and organs. The terms “tissue engineering” and “regenerative medicine” have become largely interchangeable, as the field hopes to focus on cures instead of treatments for complex, often chronic, diseases.

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Stem cells

Cells with the ability to divide for indefinite periods of time in culture (self-renewal) and give rise to specialized cells (differentiation). There are several types of stem cells defined by their characteristics and tissue source: 

  • Embryonic stem cells (ESCs): Embryonic stem cells are isolated from the inner cell mass of a 5-day pre-implantation embryo that are capable fo dividing without differentiating for a prolonged period in culture.  ESCs are also known to be pluripotent meaning that they can become any cell or tissue of the ectoderm, endoderm, or mesoderm lineage.  Human ESCs are only isolated from embryos that were generated through in vitro fertilization (IVF) and donated by the parents through a process of informed consent.
  • Adult stem cells: Also referred to as somatic stem cells, these are cells that are found in many organs and differentiated tissues that have a limited capacity for self-renewal and differentiation (multi-potent).
  • Umbilical cord stem cells: Stem cells collected from the umbilical cord at birth that can produce all of the blood cells in the body
  • Placenta-derived stem cells:
  • Bone Marrow-derived stem cells: a multi-potent population of cells found in the bone marrow that are different from blood cells and include hematopoietic and mesenchymal stem cell
  • Adipose-derived stem cells
  • Mesenchymal stem cells (MSCs): These are non-blood adult stem cells from a variety of tissues including bone marrow, adipose tissue, and umbilical cord blood and tissue
  • Hematopoietic stem cells (HSCs): a stem cell that gives rise to all red and white blood cells and platelets. These cells are found in bone marrow and umbilical cord blood.

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Biomaterials

Biomaterials may be natural or synthetic and are used in medical applications to support, enhance, or replace damaged tissue or a biological function. Metals, ceramics, plastic, glass, and even living cells and tissue all can be used in creating a biomaterial. They can be reengineered into molded or machined parts, coatings, fibers, films, foams, and fabrics for use in biomedical products and devices. These may include heart valves, hip joint replacements, dental implants, or contact lenses. They often are biodegradable, and some are bio-absorbable, meaning they are eliminated gradually from the body after fulfilling a function.

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Metabolic syndrome
Self renewal
Differentiation
Potency

The potential of a cell to differentiate; pluripotency: the ability to become all tissues of an organism, but not capable of sustaining full organismal developoment; multipotency: the ability to differentiate into cells of a defined tissue lineage.

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Immunomodulatory
Precursor cells
Cell culture