Abstract

Mesenchymal stem cells are heterogenous adult multipotent stromal cells that can be isolated from various sources including: bone marrow, peripheral blood, umbilical cord blood, dental pulp, and adipose tissue. They have certain immunomodulatory, immunosuppressive, and antimicrobial properties that enable them to have several therapeutic and clinical applications including: treatment of autoimmune disorders, role in hematopoietic stem cell transplantation and regenerative medicine, as well as treatment of various infections and their associated complications such as septic shock and acute respiratory distress syndrome. Although more success has been achieved in preclinical trials on the use of mesenchymal stem cells in animal models than in human clinical trials, particularly in septic shock and Chagas disease, more progress has been made in both disorders after the recent use of specific sources and certain doses of mesenchymal stem cells. Nevertheless, the utilization of this type of stem cells has shown remarkable progress in the treatment of few infections such as tuberculosis. The clinical application of mesenchymal stem cells in the treatment of several diseases still faces real challenges that need to be resolved. The following book chapter will be an updated review on the role of mesenchymal stem cells in various infections and their complications.

Keywords: mesenchymal stem cells, host immunity, antimicrobial properties, septic shock, Mycobacterium tuberculosis, Chagas disease, human immunodeficiency virus

#### 1. Introduction to mesenchymal stem cells

Mesenchymal stem cells (MSCs), which were first described by Alexander Fridenstein in the 1960s, are heterogeneous, non-hematopoietic, adult multipotent stromal progenitor cells that are capable of self-renewal as well as differentiation into multiple lineages and various cell types [1–8]. They can be isolated from several sources including bone marrow (BM), peripheral blood (PB), umbilical cord blood (UCB), amniotic fluid, placenta, adipose tissue (AT), and dental pulp as shown in Table 1 [1–8]. Although the BM is the main source of MSCs, these stromal cells constitute only a small fraction of the total number of cells populating the BM [2, 4–6].

MSCs have the following distinguishing features: (1) ability to adhere to the plastic vessel under optimal culture conditions; (2) capability to differentiate into osteoblasts, adipocytes, and chondrocytes; and (3) having characteristic immunophenotypic profile on flow cytometry [1–3, 5, 6, 8, 9]. MSCs are characteristically positive for: CD 105, CD 73, and CD 90 and characteristically negative for the following surface

markers: CD 45, CD 34, CD 11b, CD 14, CD 19, CD 79a, and HLA-DR. However, certain types of MSCs can occasionally show positivity or negativity for specific surface markers as shown in Table 2 [1–3, 5, 6, 8–14]. Also, MSCs can differentiate

The Rising Role of Mesenchymal Stem Cells in the Treatment of Various Infectious Complications

Several studies have shown that MSCs obtained from BM, AT, and other sources

MSCs have immunomodulatory and immunosuppressive properties that enable them to have several therapeutic and clinical applications including: hematopoietic stem cell transplantation (HSCT), autoimmune disorders, regenerative medicine and tissue repair, neurological diseases, bone and cartilage disorders, as well as treatment of several infections and acute respiratory distress syndrome (ARDS). Details are shown in Table 3 [1, 2, 6, 8, 25–29]. MSCs are major constituents of the BM microenvironment and the HSC niche and apparently they are the masters of

a. Bacterial infections including sepsis and its associated acute respiratory distress syndrome b. Viral infections such as human immunodeficiency virus, hepatitis B and C viruses c. Parasitic infections such as Chagas disease, schistosomiasis, and malaria

into other cell types including: myocytes, cardiomyocytes, and neurons [5].

discovered genes regulate stemness or only differentiation of MSCs [7].

2. Functions, properties, and therapeutic indications of MSCs

1. Hematopoietic stem cell transplantation: a. Enhancement of engraftment

DOI: http://dx.doi.org/10.5772/intechopen.91475

3. Regenerative medicine and tissue repair:

d. Mycobacterial infections such as tuberculosis

Current and potential therapeutic indications for mesenchymal stem cells.

a. Macular degeneration, corneal reconstruction and transplantation b. Bones and joints: osteogenesis imperfecta, osteoarthritis, and osteoporosis

c. Treatment of GVHD 2. Treatment of autoimmune diseases: a. Systemic lupus erythromatosus b. Rheumatoid arthritis c. Systemic sclerosis d. Type 1 diabetes mellitus e. Multiple sclerosis f. Crohn's disease

> a. Myocardial ischemia b. Cardiac dysfunction c. Chronic non-healing wounds

d. Liver injury e. Myocardial infarction f. Dilated cardiomyopathy g. Critical limb ischemia h. Spinal cord injuries 4. Treatment of various infections:

5. Other indications:

c. Cancer gene therapy d. Amyotrophic lateral sclerosis

e. Liver cirrhosis

Table 3.

31

b. Prevention of graft versus host disease (GVHD)

do express CD 34 surface markers [4, 15–18]. MSCs can be seen in abundant numbers in the circulation under the following circumstances: stem cell mobilization with growth factors, tissue injuries, stroke, hypoxia, and inflammatory conditions [4, 19–24]. Despite the efforts displayed over the last five decades including identification of nine transcriptional factors, little is known about the molecular basis underlying the stemness of MSCs and it is still unclear whether these recently


#### Table 1.

Sources of mesenchymal stem cells.


MSCs, mesenchymal stem cells; HLA, human leukocyte antigen.

The bold values are to differentiate characteristic from non-characteristic surface markers.

#### Table 2.

Surface markers of MSCs on Flow cytometry.

The Rising Role of Mesenchymal Stem Cells in the Treatment of Various Infectious Complications DOI: http://dx.doi.org/10.5772/intechopen.91475

markers: CD 45, CD 34, CD 11b, CD 14, CD 19, CD 79a, and HLA-DR. However, certain types of MSCs can occasionally show positivity or negativity for specific surface markers as shown in Table 2 [1–3, 5, 6, 8–14]. Also, MSCs can differentiate into other cell types including: myocytes, cardiomyocytes, and neurons [5].

Several studies have shown that MSCs obtained from BM, AT, and other sources do express CD 34 surface markers [4, 15–18]. MSCs can be seen in abundant numbers in the circulation under the following circumstances: stem cell mobilization with growth factors, tissue injuries, stroke, hypoxia, and inflammatory conditions [4, 19–24]. Despite the efforts displayed over the last five decades including identification of nine transcriptional factors, little is known about the molecular basis underlying the stemness of MSCs and it is still unclear whether these recently discovered genes regulate stemness or only differentiation of MSCs [7].
