**Author details**

*3.7.3. Regulation of growth factors and hormones*

118 Wound Healing - New insights into Ancient Challenges

**3.8. Limitations of using MSCs for wound healing**

49, 50, 167].

non‐healing wounds.

**4. Conclusion**

As previously described, growth mediatory factors play pivotal roles in wound healing. Therefore, more quantities of these growth factors are required to progress the healing process, in particular in case of chronic wounds, so they should be continuously upregulated [31, 32]. Several methodologies have been proposed to maintain efficient concentrations of growth factors at the injury site. Direct application of such biomolecules, however, requires large quantities and repetitive application. Spreading autologous platelets over the injury site which later secrete growth factors such as EGF, IGF‐1, IGF‐2, TGF‐β and VEGF has been proposed [165] as has the utilisation of keratinocytes and fibroblasts on a collagen matrix to enhance further secretion of growth factors when applied on the wound [32, 166]. Another potential way to protect efficient concentrations of growth factors at the wound site is through the prevention of their breakdown by analytical enzymes and thereby preventing the formation of proteases such as elastase [31, 32]. Oestrogen and prostaglandins have also been showed to play a role in the healing process; maintenance of their concentration at efficient levels may thus prevent excess neutrophils from reaching the injury site and produce more elastase [41,

MSCs can be considered as a promising tool for treating non‐healing wounds; however, some aspects of MSC biology need to be intensively studied before use in clinical application. One of these is the problem of finding a source of MSC isolation with no invasive procedure for autologous treatment, for example isolation of MSCs from peripheral blood instead of bone marrow. Other questions include the following: What is the ideal number and timing of MSC administration/implantation? How long can MSCs survive at the injury site after implantation? Are multiple administrations or implantations required for successful healing? When do the implanted MSCs start releasing their soluble secretions after implantation/administration? And finally, are the secretions of MSCs controllable? Answers to these questions are important and essential for the therapeutic use of MSCs and a safer and a more effective treatment for

Mesenchymal stem cells (MSCs) and their secretions are promising therapeutics for use in accelerating wound healing. Ease of availability, isolation and *in vitro* expansion make MSCs the best candidates for wound‐healing therapies in comparison with other stem cells including embryonic stem cells (ESCs). Two main strategies could be used in the application of MSCs to the treatment of non‐healing wounds. MSCs show the ability to differentiate into different cells of the epidermis. Also, MSC secretions collected from their *in vitro* cultures (MSC‐CM) and their small vesicles (MSC‐EXOSOME) are important for promoting proliferation and migration of skin cells, such as keratinocytes and fibroblasts, into the injury site. MSC‐CM contains a wide range of at least 36 known growth factors, and cytokines work in synergy to accelerate Moyassar B. H. Al‐Shaibani1,2\*, Xiao‐nong Wang1 , Penny E. Lovat1 and Anne M. Dickinson1

\*Address all correspondence to: m.b.h.al‐shaibani@newcastle.ac.uk

1 Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK

2 Department of Medical Biotechnology, College of Biotechnology, Al‐Nahrain University, Baghdad, Iraq
