Stem cells are a group of cells with multi-directional differentiation and self-replication ability.

A cell that turns into a variety of different functions is "multidirectional differentiation"; a cell becomes several to ten million cells, which is "self-replication." During embryonic development, stem cells differentiate into a wide variety of cells and further form various complex tissues and organs. After the individual matures, the stem cells still exist in various parts of the body, including the brain, heart, bone marrow, teeth, peripheral blood, fat, etc., to function as cell renewal and damage repair of tissues and organs.

Stem cells can be divided into four categories based on differentiation potential:

1. Totipotent stem cells

A totipotent stem cell refers to a stem cell that has "complete ability." It can differentiate into any adult tissues and can gradually develop into a complete individual. For example: fertilized eggs.

2. Pluripotent stem cells

The pluripotent stem cells can form cells of various tissues of the human body, but cannot develop into individuals by themselves. For example: embryonic stem cells.

3. Multipotent stem cells

Multipotent stem cells can only differentiate into cells of certain tissues, such as hematopoietic stem cells, which can differentiate into blood cells and immune cells. Such stem cells are not free to develop into other tissues and intact individuals.

4. Unipotent stem cells

Unipotent stem cells can only differentiate into a single cell, but still have the ability to self-renew, for example, lymphoblasts can differentiate into lymphocytes. Unipotent stem cells are also known as precursor cells, progenitor cells, or blasts.

Stem cells can be divided into two categories based on the sources of acquisition:

1. Embryonic stem cell

The source of embryonic stem cells is the cell mass in the embryo, which is distinguished by the ability to develop into a variety of different cellular tissues required for a complete living individual. However, embryonic stem cells have few sources of acquisition, and there are also risks such as cell variability and carcinogenicity, and involve very large moral controversies. Currently, only a very small range of studies are allowed in countries around the world.

2. Adult stem cells

Adult stem cells are cells that remain in fetal and adult tissues and organs and still retain the ability to grow and differentiate into other cell types. After people being born, adult Stem Cells (ASCs) maintain their health and function. Under normal circumstances, adult stem cells are at rest. When the human body is damaged, adult stem cells will become precursor cells of the injured site and repair damage. Since adult stem cells do not involve moral and ethical problems, and they will not cause immune rejection in the future, the current research direction in the world is mainly adult stem cells.

There are many types of adult stem cells, among which hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) have been studied for many years. The main function of hematopoietic stem cells is to differentiate into different blood cells including red blood cells, platelets and various white blood cells. The main function of mesenchymal stem cells is to differentiate into cells other than blood cells, such as bones, fat, muscles, nerves and the like.

Adult stem cells exist in various organs and tissues of the body. Among them, a large number of cells (both hematopoietic stem cells and mesenchymal stem cells) can be obtained in the bone marrow. However, direct extraction of bone marrow requires general anesthesia with high invasiveness and hospitalization observation. The recovery is slower and the risk is greater. The rest are stem cells obtained by collecting cord blood or peripheral blood. The former is limited by the amount of cord blood, although cord blood also contains hematopoietic stem cells and mesenchymal stem cells, the amount of cells is small because of the small amount of blood.

Peripheral blood stem cells (PBSCs) are currently obtained by first applying G-CSF to mobile stem cells to move out of the bone marrow and release them into the peripheral blood, so that the number of stem cells in the peripheral blood is increased by a hundredfold, and then separate stem cells using peripheral blood stem cell apheresis system. This process is similar to blood donation with high safety, great number and variety of cells obtainment, good quality, wide application and low side effects. Therefore, the source of adult stem cells is mainly from peripheral blood collection.

In addition to adult stem cells, VSEL™ (Very Small Embryonic-like Stem Cells) has attracted worldwide attention in recent years. In 2006, Dr. Mariusz Ratajczak, director of the Stem Cell Research Institute at the James Graham Brown Cancer Center at the University of Louisville in the United States, discovered that there is a rare number of pluripotent stem cells in the bone marrow, which are very small and have the differentiation ability similar to Embryonic Stem Cells (ESC). Therefore, it is named VSEL™ (Very Small Embryonic-like Stem Cells). Scientists have found that VSEL™ has been stored in the human body from a dormant state during embryonic development. When the body tissue is injured, it mobiles to the peripheral blood to help repair damaged tissue, and has the ability to rebuild multiple tissues. . Many clinical trials in the United States have also demonstrated that VSEL™ can repair damaged myocardium in patients with myocardial infarction. Scientists believe that VSEL™ can achieve the same positive benefits of embryonic stem cells without falling into the ethical and moral dilemmas of embryonic stem cells. The relevant technology and patents of VSEL™ are exclusively owned by Caladrius Biosciences worldwide.

Comparison of stem cells commonly asked

At present, the market is full of different sources and information of stem cells. Inaccurate and asymmetric information has caused great risks and application restrictions. Embryonic stem cells have the risk of allogeneic rejection and canceration and have great moral controversy; iPS can not control the speed and quantity of cell differentiation and could lead to cell mutation; adipose stem cells have great risks of surgery and postoperative complications and limited effect, etc.

TYPE	ORIGIN	EXTRACTION METHOD	RISK ANALYSIS
Embryonic Stem Cell (hESC)	Inner Cell Mass (ICM) of Embryo (Allogenic)	Cultivate the inner cell mass in the fertilized egg	- Scarce source - Risk of cell variability and carcinogenicity - Great moral controversy
induced Pluripotent Stem Cell (iPS)	Induced from Epidermic Cell (Autologous)	Made from genetically introduced into adult cells	- Low successful rate in induction - Risk of cell variability and carcinogenicity
Dental Pulp Stem Cells (hDPSCs)	Deciduous teeth, gums, periodontal ligaments, wisdom teeth (Autologous)	Natural loss (deciduous teeth) or mannually obtained (gum, periodontal ligament, wisdom tooth)	- Single cells with limited applicability - The number of cells is too low and still needs to be expanded when needed
Bone Marrow Stem Cell (BMSC)	Bone Marrow (Autologous/ Allogenic)	Bone marrow aspiration	- Bone marrow puncture surgery requires general anesthesia, high risk of invasiveness - The wound is susceptible to infection and requires hospitalization for a longer recovery time. - Limited number of cells and punctures
Adipose Mesenchymal Stem Cell (AD-MSC)	Fat (Autologous)	Liposuction (surgical) procedures	- Single cells with limited applicability - Poor differentiation ability - The number of cells is too low and still needs to be expanded when needed - Wounds are susceptible to infection - Longer recovery time after surgery
Umbilical Cord Mesenchymal Stem Cell (UC-MSC)	Umbilical cord (Autologous/ Allogenic)	Obtained during childbirth	- Single cells with limited applicability - Young and potent cells with strong differentiation ability
Placenta Mesenchymal Stem Cell (P-MSC)	Placenta (Autologous/ Allogenic)	Obtained during childbirth	- Single cells with limited applicability - Young and potent cells with strong differentiation ability
Amniotic fluid mesenchymal stem cells (AF-MSC)	Amniotic fluid (Autologous/ Allogenic)	Obtained during amniocentesis between 16 and 20 weeks of pregnancy	- Single cells with limited applicability - Young and potent cells with strong differentiation ability
Peripheral Blood Stem Cell (PBSC)	Peripheral blood (Autologous)	Apheresis procedures	- Contains diverse stem cells - Individual differences will directly affect the number of PBSC harvested, such as response to G-CSF, physical condition, etc.