**Author details**

secretome-mediated repair will contribute to the development of new regenerative therapies

Recently, the great potential of tissue engineering and regenerative medicine strategies for bone augmentation has been demonstrated, and the feasibility of using CM from MSC as an osteoinductive agent for future clinical use is becoming more evident. CM from bone marrow-MSC increased the migration and proliferation of MSCs, vascularization and the early bone regeneration in rabbit sinus model, showing CM as a promising novel therapeutic agent to promote bone regeneration after maxillary sinus floor elevation [91]. It has been shown that CM can have stronger effects than MSCs, accelerating the mobilization of endogenous endothelial and MSC cells for bone regeneration in rat calvarial bone defect model [92]. Intravenous administration of MSC-CM provided the protection of osteoblasts and osteoclasts, induced angiogenesis, anti-apoptotic and anti-inflammatory effects in a rat bisphosphonaterelated osteonecrosis of the jaw-like model [93]. It has also been reported that the use of MSC-CM may be an alternative therapy for periodontal tissue regeneration [94]. CM from human MSC accelerates the formation of new bone callus, shortening the time period required for distraction osteogenesis treatment in a mouse model by recruiting endogenous mouse bone

marrow stem cells (mBMSCs) and EC/EPCs via MCP-1/-3 and IL-3/-6 signaling [95].

We have also reported that human Ad-MSCs and their CM induce bone regeneration in a jaw rabbit model, and that morphometric, radiographic and histological analysis demonstrate that the amount and quality of neoformed bone, repaired area, bone density, arrangement of collagen fibers, maturation and inorganic matrix calcification are very similar between Ad-

All the scientific evidence on the paracrine effect of MSC provide the opportunity to exploit the therapeutic potential of MSC-CM and opens up scenarios for the identification of new candidate molecules for tissue repair via proteomic analysis of the MSC secretome. MSC-CM delivers osteoinductive growth factors and cytokines that modulate the behavior of endoge‐ nous cells contributing to the formation of new tissue. Furthermore, the use of MC allows us to avoid some of the limiting factors associated with the clinical application of stem cells, such as the risk of tumorigenesis and transmission of infectious diseases [80], immunological

The use of MSC-CM as a novel therapeutic strategy has several practical advantages. CM storage and transportation procedures are not as complex as they are for MSC. CM production can be less expensive, enabling access to disadvantaged populations and reducing costs for

Despite the advantages of its use, CM application may not always supersede the use of MSC, and it is possible that for some type of disorders MSC could be a more effective alternative. The number of known molecules mediating the paracrine effect of MSC grows every day, and

incompatibility, costs and waiting time for cell ex vivo expansion [80].

significantly increases the potential range of their therapeutic applications.

that will not require cell transplants [90].

266 Advanced Techniques in Bone Regeneration

MSC and CM-treated groups [21] (**Figure 3**).

**5. Perspectives**

health systems.

Orlando Chaparro\* and Itali Linero

\*Address all correspondence to: ochaparrog@unal.edu.co

Universidad Nacional de Colombia, Facultad de Medicina - Facultad de Odontología Biología de Células Madre, Ciudad Universitaria, Bogotá, Colombia
