All Things Stem Cell

While there is great potential for using stem cells in regenerative therapies, there is still a ways to go before it can be considered a proven practice, although recent breakthroughs, and one specific trial in particular, makes it seem much closer. Recently, the first human tissue-engineered organ using stem cells was created and transplanted successfully into a patient. Other tissue regeneration efforts with stem cells have also recently made many breakthroughs, emphasizing the potential of using stem cells in future tissue transplants.

In the first reported instance of using stem cells to bioengineer a functional human organ, Paolo Macchiarini and his research group used a patient’s own stem cells to generate an airway, specifically a bronchus, and successfully grafted it into the patient to replace her damaged bronchus (See Figure 1). Macchiarini’s group bypassed the problem of immune rejection by using the patient’s own stem cells. Additionally, by combining a variety of bioengineering efforts, no synthetic parts were involved in the creation of the organ; it was made entirely of cadaveric and patient-derived tissues (Macchiarini et al., 2008; Hollander et al., 2009).

Figure 1. In order to create a patient-compatible replacement bronchus, Macchiarini’s group removed and decellularized a trachea from a cadaveric donor, grew cells removed from the patient on the trachea in a bioreactor, and then transplanted the bioengineered airway into the patient, successfully replacing their defective bronchus (Macchiarini et al., 2008).

Read more…

admin Bioengineering, Mesenchymal Stem Cells adult, clinical trials, mesenchymal, regenerative medicine

Often the feasibility of using stem cells for regenerative therapies is limited by two factors: obtaining a significant number of cells and doing so in a relatively noninvasive manner. Because our bodies freely shed a limited and select number of cells, many stem cell types must be obtained using a rather invasive procedure. However, around the beginning of last year two laboratories independently reported the discovery of a new type of stem cell that may overcome both obstacles; stem cells were found to reside in menstrual blood (Meng et al., 2007; Patel et al., 2008). These stem cells, termed endometrial regenerative cells (ERCs), are not only harvested in a noninvasive manner and relatively readily available in large quantities, but they potentially overcome the problem of immune rejection in many female patients as well.

The uterus is lined by a layer of cells called the endometrium. During the menstrual cycle, the endometrium cycles between thickening and being broken down if fertilization does not occur. The break down and expulsion of the endometrium is called menstruation, or menstrual bleeding, and is the source of endometrial regenerative cells (ERCs).

Researchers suspected stem cells to be present in menstrual blood because stem cells were previously found to be present in the lining of the uterus. The wall of the uterus is lined by a layer of cells called the endometrium (see figure). To create ideal conditions for the uterus to accept and nurture an embryo, the endometrium lining becomes thicker and increases the number of blood vessels and glands within it. However, if implantation does not occur, the endometrium lining is broken down and shed. Overall, the endometrium is quite a hyperproliferative tissue, continuously being broken down and rebuilt; it is an ideal tissue to investigate for the presence of stem cells. In the menstrual cycle, the shedding is known as menstruation, or menstrual bleeding; the excreted menstrual blood is made up of blood as well as cells from the endometrium layer. Researchers previously reported the presence of stem cells in the intact endometrium lining of the uterus (Cho et al., 2004; Schwab et al., 2005; Du and Taylor, 2007). Because stem cells were found in the endometrium, researchers thought it likely that stem cells could also be found in the shed endometrium in the form of menstrual blood, which can be obtained in relatively large quantities in a much less invasive manner. However, the stem cells discovered in menstrual blood, ERCs, appear to be rather different from stem cells derived from the intact endometrium.

While stem cells from the intact endometrium appear to be mesenchymal stem cells (MSCs, as discussed earlier), ERCs do not; they are distinctly different not only in their undifferentiated state, but in the cells they can differentiate into as well. Researchers categorize stem cells into certain groups based off of, among other factors, their cell morphology and the proteins they express. An established stem cell group usually expresses a distinct set of proteins. ERCs, though morphologically appearing mesenchymal, were found to express only some, but not all, proteins characteristic of MSCs. Additionally, ERCs were reported to be able to differentiate into, or become, cells from the three different germ layers (see the previous post on MSCs for more details): mesoderm (muscle, bone, fat, cartilage, and endothelial cells), ectoderm (neurons), and endoderm (liver, pancreas, and lung cells) (Meng et al., 2007; Patel et al., 2008). However, the mesenchymal stem cells from the intact endometrium cannot generate cells from all three germ layers. Overall, ERCs were determined to be functionally distinct from endometrium MSCs (Meng et al., 2007; Hida et al., 2008).

Read more…

admin Endometrial Regenerative Cells adult, clinical trials, embryonic, hematopoietic, mesenchymal, news, regenerative medicine

Perhaps containing more different cell types than any other stem cell category, mesenchymal stem cells (MSCs) can be isolated from a wide variety of tissues in the human body. These cells have been grouped and labeled as “mesenchymal” because they are thought to have a common progenitor in the mesenchyme, an embryonic tissue (Caplan, 2005). In the developing vertebrate embryo, there are three distinct “germ layers,” or layers of cells: the endoderm, the mesoderm, and the ectoderm. Together with the germ cells, these three layers pattern out the entire body (see figure). The mesenchyme is a collection of cells mostly derived from the mesoderm that later becomes supportive structures throughout the body, including bone, cartilage, connective tissue, smooth muscle, adipose tissue, as well as the lymphatic and hematopoietic systems. Most MSCs are thought to contain progenitors in the mesenchyme (Gilbert, 2003; Conrad et al., 2009; Caplan, 2005).

The endoderm layer later becomes skin (epidermis) and the nervous system, the ectoderm becomes the digestive tract and respiratory system, and the mesoderm becomes bone, blood, muscles, connective tissue, and several organs (heart, kidney, and gonads).

However, calling MSCs “mesenchymal” can be misleading. Because this term refers to a precursor of the large MSC family, it is referring to an embryonic tissue, though the descendant MSCs can be found in both fetal and adult tissues. MSCs have been isolated from adult muscle, bone marrow, adipose tissue, cartilage, bone, potentially teeth (Caplan, 2005) as well as some fetal tissues (fetal liver, lung, amniotic fluid, and umbilical cord) (Phinney and Prockop, 2007). The MSCs isolated from any one of these tissues are multipotent and are usually shown to be MSCs by being able to differentiate into at least three different, standard mesenchymal cell types: osteocytes (bone), chondrocytes (cartilage), and adipocytes (fat) (Baksh et al., 2004). There is much evidence, though somewhat inconsistent, showing that MSCs can also differentiate into neuronal cells, which may be from mesenchyme derived from the endoderm instead of the mesoderm (Gilbert, 2003; Phinney and Prockop, 2007). Overall, MSC differentiation potentials can vary depending on what mesenchyme-derived tissue the MSCs were harvested from (Phinney and Prockop, 2007). However, MSCs cannot become hematopoietic cells (which are derived from hematopoietic stem cells), even though these cells are derived from the mesenchyme, making the label “mesenchymal” more deceptive (Gilbert, 2003; Caplan, 2005).

Read more…

admin Mesenchymal Stem Cells adult, embryonic, hematopoietic, history, mesenchymal, regenerative medicine

The tooth is made up of four primary components: dental pulp, dentin, enamel, and cementum (Cate, 1998)

A relatively recent addition to the stem cell family and holding promise as an easily obtained source of adult stem cells, dental pulp stem cells (DPSCs) were discovered at the beginning of this decade (Gronthos et al., 2000). DPSCs, also known as SHED cells (stem cells harvested from exfoliated deciduous teeth (Miura et al., 2003)), are one of the few discovered stem cells available from a naturally molted human tissue.

Dental pulp, which is living tissue at the center of the tooth made up of cells called “odontoblasts,” contains the aptly-named DPSCs. DPSCs were originally identified as being able to produce odontoblast-like cells as well as a tissue similar to dentin, which normally surrounds and protects the dental pulp (Gronthos et al., 2000; 2002). Although these studies found DPSCs able to produce two of the primary components of teeth, pulp and dentin, studies have not reported that DPSCs are able to create the other two factors, which are enamel and cementum (Cate, 1998).

Read more…

admin Dental Pulp Stem Cells adult, history, mesenchymal, neural crest, news, regenerative medicine