Stem Cells 101

What Are Stem Cells?
Stem cells are distinguished from other cell types by two important characteristics: 1) They are unspecialized cells capable of continually renewing themselves through cell division and 2) they have the potential to develop into many different cell types of the body. Given their regenerative potential, stem cells offer new opportunities for treating diseases.
Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell. (NIH)
Do I have stem cells in my body?
Yes. Stem cells are the foundation cells for our bodies. The highly-specialized cells that make up our organs and tissues originally come from an initial pool of stem cells that formed shortly after fertilization. Throughout our lives, we continue to rely on persisting stem cells to repair injured tissues and replace cells that are lost every day, such as those in our skin, hair, blood and lining of our gut. (ISSCR)
Why are stem cells important?
Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lungs, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.
Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine. (NIH)
What are the different types of stem cells?
There are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells, which exist only at the earliest stages of development and various types of “tissue-specific” or “adult” stem cells that appear during fetal development and remain in our bodies throughout life. In addition, scientists have recently been able to create induced pluripotent stem cells or IPS cells in the laboratory. These cells, which are not found in the body but rather are engineered from specialized cells, such as those from skin, have properties similar to those of embryonic stem cells. (ISSCR)
Embryonic stem cells, as their name suggests, are derived from embryos. Most embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro—in an in vitro fertilization clinic—and then donated for research purposes with informed consent of the donors. They are not derived from eggs fertilized in a woman’s body (NIH)
An adult stem cell is thought to be an undifferentiated cell, found among differentiated cells in a tissue or organ. The adult stem cell is multipotent meaning it can renew itself and can differentiate to yield some or all of the major specialized cell types of the tissue or organ. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Scientists also use the term somatic stem cell instead of adult stem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs). Unlike embryonic stem cells, which are defined by their origin (cells from the preimplantation-stage embryo), the origin of adult stem cells in some mature tissues is still under investigation.
Research on adult stem cells has generated a great deal of excitement. Scientists have found adult stem cells in many more tissues than they once thought possible. This finding has led researchers and clinicians to ask whether adult stem cells could be used for transplants. In fact, adult hematopoietic, or blood-forming, stem cells from bone marrow have been used in transplants for more than 40 years. Scientists now have evidence that stem cells exist in the brain and the heart, two locations where adult stem cells were not at first expected to reside. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-based therapies. (NIH)
Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem cell–like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers. (NIH)
Are Longeveron Stem Cells Embryonic Stem Cells?
No. Longeveron is using adult donor stem cells.
What are the potential uses of human stem cells?
There are many ways in which human stem cells can be used in research and the clinic. Human stem cells are currently being used to test new drugs. Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including macular degeneration, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis. For example, it may become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research in mice and other animals indicates that bone marrow stromal cells, transplanted into a damaged heart, can have beneficial effects. Whether these cells can generate heart muscle cells or stimulate the growth of new blood vessels that repopulate the heart tissue, or help via some other mechanism is actively under investigation. For example, injected cells may accomplish repair by secreting growth factors, rather than actually incorporating into the heart. Promising results from animal studies have served as the basis for a small number of exploratory studies in humans (NIH)
What type of stem cells is Longeveron using, and where do they come from?
Longeveron’s stem cells are “adult” or “tissue-specific” allogeneic mesenchymal stem cells harvested from the bone marrow of adult human donors, and then produced at the Longeveron processing facility. We refer to them as LMSCs.
What is regenerative medicine?
The goal of regenerative medicine is to repair organs and tissues that are damaged by disease, aging or trauma, such that function is restored or improved. The term regenerative medicine is often used nowadays to describe medical treatments and research that use stem cells to restore the function of organs or tissues. This can be achieved in different ways; first, by administering stem cells, or specific cells that are derived from stem cells in the laboratory; or second, by administering drugs that coax stem cells that are already present in tissues to more efficiently repair the tissue involved.
Are stem cells currently used in therapies?
A bone marrow transplant, also called a hematopoietic stem cell transplant, is a medical procedure used to treat conditions of the blood such as leukemia, sickle cell anemia or some metabolic conditions. It relies on the hematopoietic (blood) stem cells that are present in the bone marrow that are the precursors to all blood cells. Doctors have been transferring blood stem cells by bone marrow transplant for more than 40 years. Advanced techniques for collecting or “harvesting” blood stem cells are now used. Cord blood, like bone marrow, is stored as a source of blood stem cells and is used as an alternative to bone marrow in transplantation. Other stem cell applications are the use of skin progenitor cells for burns and the use of limbal stem cells, which reside in the cornea, for injury of the cornea. With the exception of the treatments discussed here, the use of cell therapies remains at an experimental stage. (ISSCR) Longeveron is currently conducting clinical trials for application of LMSCs to several conditions.

Glossary

Allogeneic
denoting, relating to, or involving tissues or cells that are genetically dissimilar and hence immunologically incompatible, although from individuals of the same species.
Cytokine
Any of a number of substances, such as interferon, interleukin, and growth factors, that are secreted by certain cells of the immune system and have an effect on other cells.
Endothelial dysfunction
(considered a cardiovascular risk factor) In vascular diseases, a systemic pathological state of the endothelium (the inner lining of blood vessels) and can be broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by (or acting on) the endothelium.
Endothelial Progenitor Cells
A term that has been applied to multiple different cell types that play roles in the regeneration of the endothelial lining of blood vessels.
Immunoprivileged
(when referencing a cell or area of the body) able to tolerate the introduction of antigens without eliciting an immune response
Immunosenescence
The gradual deterioration of the immune system brought on by natural age advancement. It involves both the host’s capacity to respond to infections and the development of long-term immune memory, especially by vaccination.
Macrovascular
An adjective referring to the large blood vessels, including the coronary arteries, the aorta, and the sizable arteries in the brain and in the limbs.
Multipotent Stem Cells
Stem cells that have the ability to develop into more than one cell type of the body.
Regenerative Medicine
A field of medicine devoted to treatments in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cell populations or tissues.
Tumor Necrosis Factor Alpha
(TNF-alpha) a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.

Longeveron Stem Cells

What makes our stem cells unique?
Longeveron-produced allogeneic mesenchymal stem cells (LMSCs) are created from adult human bone marrow mesenchymal stem cells (MSCs) using our proprietary technology. LMSCs are powerful multipotent regenerative and restorative cells that modulate the immune system.