**7. Stem cells and decellularized scaffolds**

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

A clinical study by Centeno and colleagues reported the application of culture-expanded, autologous BM-MSC for osteoarthritis in more than 300 patients. The authors reported the safety and efficacy of its use. Briefly, the autologous BM-MSCs were cultured in monolayer culture flasks and transplanted into the affected peripheral joints. They concluded that a 50% improvement in clinical symptoms was recorded among the osteoarthritis patients [27]. The application of infrapatellar fat pad-derived ASCs was demonstrated by Koh and colleagues when they reported its efficiency in improving and managing knee osteoarthritis through

A mixture of stem cells and progenitor cells with CD90- and CD14-expressing cells resident in the bone marrow called tissue repair cells (TRC) has been demonstrated to be efficient for reconstructing craniofacial bone defects in a controlled feasibility trial [29]. Briefly, the clinical trial was carried out using 24 patients in need of localized osseous reconstruction. The patients were randomized to either guided bone regeneration (GBR) or TRC transplantation and were subsequently assessed. They concluded that TRC therapy resulted in an accelerated

**5. Induced pluripotent stem cells seeded for bone tissue engineering**

Yamanaka's group is one of the pioneers of studies related to induced pluripotent stem cells. Yamanaka et al. studies like [30] where they reported the possibility of reprogramming of somatic cells into a primordial embryonic stem cell-like state, capable of differentiating into all three germ layers. There are several studies demonstrating the application of iPSCs in tissue engineering like [31], where they reported the ability of polyethersulfone scaffolds seeded with iPSCs to regenerate cranial bone. The authors concluded that iPSCs seeded with polyethersulfone scaffolds promoted and stimulated cranial bone formation compared to scaffold alone. In similar scaffold study design, Liu used an Arg-Gly-Asp-grafted calcium phosphate cement scaffold seeded with iPSC-MSCs overexpressing NELL1 that were efficient to improve osteogenic differentiation process [32]. However, this report was challenged by [33] reporting that osteogenic abilities of iPSCs can only be realized by scaffolds fabricated with calcium phosphate alone in an ex vivo model. The use of iPSCs in tissue engineering has been reported using animal model by Lian and colleagues, in their mouse model of limb ischemia study. They reported that iPSC-MSCs were more efficient compared to adult BM-MSCs [34] based on their more efficient survival and engraftment abilities after transplantation to induce tissue regeneration.

and improved alveolar bone regeneration compared to GBR therapy.

was significant formation of blood vessel formation compared to the control [25].

**4. Clinical reports on stem application of bone tissue engineering**

clinical and radiological results [28].

126 Tissue Regeneration

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 promising clinical results.



cells and non-seeded decellularized scaffolds. The authors concluded that MSC-seeded scaffold exhibited a high level of survival of the cells and epithelialization as well as a high level of elastin. In another study on decellularized tissue, Nichols and colleagues fabricated acellular pig scaffolds using decellularized scaffold seeded with murine embryonic stem cells, pig bone marrow-derived mesenchymal stem cells, and primary human alveolar epithelial type II cells [45]. They concluded that there were recorded changes in type I collagen levels and evidences

Recent Advances in Stem Cell and Tissue Engineering http://dx.doi.org/10.5772/intechopen.75967 129

**10. Clinical application of tissue-engineered trachea and stem cells**

There have been some reports on the successful implantation of bioengineered tissues like tracheal seeded with stem cells clinically. Macchiarini and colleagues first reported the fabrication of human tissue-engineered trachea seeded with autologous epithelial cells and mesenchymal stem cell-derived chondrocytes. They reported that the engineered scaffold was later transplanted into a bronchomalacia patient to replace her left main bronchus. They concluded that there were evidences of functional airway activities and improved mechanical

In another clinical report by Otti and co-workers following a 5-year study, transplanted tracheal graft exhibited excellent vascularization and recellularization with respiratory epithelium and normal ciliary functions [59]. However, the authors also reported that because of longer production period of the tracheal graft, it might not be suitable for patients in need of urgent transplantation. In a quest to produce a tracheal graft with reduced production time, Baiguera and colleagues designed a human tracheal graft with production period of 3 weeks. The authors reported that the fabricated graft still possess structural and mechanical proper-

In another innovative clinical study carried out by [60], the authors replaced an adult airway with a stem cell-seeded decellularized tracheal scaffold in a patient suffering from congenital tracheal stenosis. They concluded that the graft scaffold showed accelerated revascularization followed by epithelialization after 12 months. Recently, human-derived decellularized trachea seeded with stem cells was demonstrated to be efficient in terms of stability, epithelialization, neovascularization, and chondrocytes formation in a patient suffering from tracheal stenosis [61].

Adipose tissue is an important constituent of soft tissues in the body that offers protection to underlying structures. Tissue flap procedures are said to be more efficient in producing a more natural reconstruction; however it is very invasive, while breast implants have been associated with complications like extrusion and lack of contraction of the breast capsule. Adipose-derived stem cells (ASCs) have been identified to be the leading candidate for breast reconstruction, although ASC supplementation has been studied in clinical trials for wound

of cell attachment and viability.

properties of the scaffold within 4 months [58].

**11. ASCs and breast tissue regeneration**

ties similar to native trachea [47].

healing therapies [62].

**Table 1.** Applications of tissue-engineered scaffolds recellularized with stem cells.
