**3. Advances in MSCs and tissue engineering technology**

The stem cells are capable of differentiating into several types of tissues and organs, while the bio-fabricated scaffold provides structural support to the seeded stem cells. Signaling factors are responsible for influencing cell phenotype, metabolism, migration, and organization.

Stem cells are undifferentiated cells of embryonic, fetal origin, and they possess the ability to give rise to differentiated cells and then finally develop into organs. Stem cell characteristics include the ability to self-replicate and renew, clonage forming, and high potency ability [1]. In terms of the potency ability of stem cells, stem cells can be totipotent, could differentiate into any cell types (pluripotent) [2], and could differentiate into cells that arise from the three

Stem cells can be categorized broadly into embryonic and adult stem cells and are efficient cell sources for tissue regenerative applications. They have also been reported to have the abilities to promote tissue homeostasis, growth, and repair, thereby contributing importantly to tissue and organ regeneration [4]. Bio-fabricated scaffolds consist of decellularized biomaterials to provide structural and anatomical functions to the seeded stem cells, thereby resulting into successful formation of specific tissue. In support of the above report, Kang and colleagues demonstrated that decellularized scaffolds loaded with autologous adipose-derived stem cells (ADSCs) were efficient to repair cartilage defect in an animal model [5]. They concluded that decellularized scaffolds loaded with ADSC induced significant and improved cartilage

MSCs are stromal stem cells that are heterogeneous and are derived from several tissue sources that include adipose tissue [6], periodontal ligaments [7], bone marrow (**Figure 1**) [8], umbilical cord (UC) [9], placenta [10], and lungs [11]. MSCs express surface markers like CD73, CD44, CD90, and CD105. The most widely known and used MSCs are bone marrow MSCs and adipose tissue-derived MSCs isolated and purified from the bone marrow and adipose tissue, respectively. Briefly, the anatomy of the bone marrow is made up of the parenchyma and the stroma part. The parenchyma houses the hematopoietic stem cells, and the stoma part consists of the bone marrow stromal cells (MSCs) that have the capability to differentiate into several cell lines like osteoblasts, chondrocytes, adipocytes, etc. The clinical use of both bone-derived mesenchymal stem cells and adipose stem cells in bone tissue engineering has been reported using various models of bone regeneration such as osteogenesis [12, 13], long bone defects [14, 15], and calvarial defects [16, 17]. Furthermore, co-administration of stem cells with cytokines has been reported to be efficient in bone repair as cytokines and growth factors like stromal derived factor-1 (SDF-1) can lead to increased migration and homing of stem cells to the defected site [18]. In a similar report by Ho et al., they demonstrated that co-administration of stromal-derived factor-1 with BM-MSCs would indirectly enhance bone repair by improving migration of innate cells to the site of bone fracture. They concluded that BM-MSCs overexpressing SDF-1 were efficient in improving the new bone formation during the early stage of fracture healing compared to BM-MSC treatment alone [19]. Genes implicated in fracture healing such as osterix [20], hypoxia-inducible factor-1 [21], and BMP-7 [22] have all been reported to be efficient in bone formation when transfected with MSCs.

germ layers—ectoderm, endoderm, and mesoderm—from which organs develop [3].

**2. Mesenchymal stem cells seeded for bone tissue engineering**

tissue repair compared to native cartilage.

124 Tissue Regeneration

Recently, bone tissue engineering in combination with novel stem cell-based technologies is yielding promising results as reported by Syed-Picard and colleagues in their experimental study that BM-MSC-derived cell sheets could be used to fabricate functional periosteal tissue [23]. Briefly, culturing BM-MSCs to hyperconfluence to produce abundant extracellular matrix to form robust cell sheets generated the BM-MSC-derived cell sheets. The authors reported that the generated cell sheets supported with calcium phosphate pellets were transplanted subcutaneously into mice for 8 weeks. They concluded that there was significant bone-like tissue formation by the BM-MSC-calcium phosphate pellet structure compared to the non-seeded calcium phosphate scaffold.

In another similar study by [24], BM-MSC cell sheet technology was compared to control cell complex. The authors reported that BM-MSC cell sheet resulted into significant expressed levels of growth factors crucial to bone development like vascular endothelial growth factor and PDGF.In another innovative study of stem cell application in tissue engineering, Ren et al. fabricated and demonstrated a three-dimensional vascularized stem cell sheet construct, composed of both BM-MSCs and human umbilical vein endothelial cells. The authors concluded that there was significant formation of blood vessel formation compared to the control [25].

**6. Endothelial progenitor cells (EPCs) seeded for bone tissue** 

tion at the site of injury compared to the unseeded scaffold [38].

**7. Stem cells and decellularized scaffolds**

MatrACELL-processed human acellular dermal matrix

3D porous urinary bladder

Decellularized porcine pulmonary valves

acellular matrix

promising clinical results.

**Organ/tissue engineered**

Skin tissue engineering

Urethral tissue engineering

Bone tissue engineering

Cardiac tissue engineering

CD34(+) cells were used in successful tibial autologous bone grafting [39].

EPCs are bone marrow-derived precursor cells and express CD34 molecules. They have the ability to differentiate into endothelial cells and ultimately contribute to the process of angiogenesis [35]. They have been reported to be resident cells in the peripheral blood and potentially contribute to the initiation of neovascularization [36]. There have been several studies demonstrating the use of EPCs in tissue engineering. Zigdon-Giladi and co-workers in their nude mouse model study with calvarial defect demonstrated that human EPCs could enhance the processes of vasculogenesis and osteogenesis [37]. They concluded that there was a significant increase in blood vessel density as well as increased extra-cortical bone height and length in the human EPC-transplanted group compared to the control. Furthermore, EPCs seeded on Gelfoam scaffold were reported to be efficient in stimulating cranial bone forma-

In a clinical case carried out by Kuroda and colleagues of tibial surgery, the efficacy of EPCs was demonstrated when autologous, granulocyte colony-stimulating factor (GCSF)-mobilized

Recently, scaffolds have been designed in the form of decellularized tissues and organs and are commonly used in tissue engineering and regenerative medicine (**Table 1**). Recent and novel advancement in tissue engineering has been the bedrock for the functional replacement of whole organs. Several organs have been bioengineered and implanted into laboratory animal recipients and potentially showing regenerative abilities and functions. Both acellular and decellularized scaffolds have been seeded with stem cells and potentially have exhibited

**Decellularized scaffolds Cells Type of** 

stem cells

Autologous bone marrow mesenchymal stem cells

Decellularized bone cylinders Human-induced pluripotent

Decellularized bone scaffolds Human adipose-derived stem cells

**experiment**

Recent Advances in Stem Cell and Tissue Engineering http://dx.doi.org/10.5772/intechopen.75967 127

In vitro and in vivo

In vitro [43]

In vivo [44]

clinical

NA In vivo and

NA Clinical [41]

**References**

[40]

[42]

**engineering**
