Development of a Novel Intra-operative Tissue Engineering Concept Using Freshly Isolated Adipose Stem Cells and Synthetic BoneSubstitutes

Background and Aim: The sources of cells used in regenerative medicinecan vary. Of the cells used, stem cells or progenitor cells (regenerationcompetentcells) have been recruited from the tissue surrounding theimplanted tissue construct, or can be harvested from well-known stemcell sources such as bone marrow, skin, muscle, and adipose tissue.Adipose tissue has several advantages over the commonly used bonemarrow, such as easy accessibility, minimal morbidity upon harvest,and an abundant, clinically relevant stem cell number which potentiallyeliminates the need for in vitro expansion. Based on this, we haveformulated an innovative surgical concept, the so-called one-step surgicalprocedure. This concept seems to be cost-effective and beneficial to thepatient. In this line, the optional use of expensive recombinant growthfactor(s) is reduced to a minimum, and a second surgical interventionis avoided while expensive contamination-sensitive stem cell expansionand specialized laboratories are not required. In addition, this conceptmight reduce donor site morbidity resultant from the graft harvesting.Methods: In a parallel process, the surgeon performs the normal surgicalprocedure while the tissue engineer processes the adipose tissue andprocures the stromal vascular fraction (SVF) containing the adipose stemcells (ASCs). Either or not, the SVF can be stimulated fora n ultrashortperiod (10-30 minutes) with a physiological dose (10 ng/mL) of aninducing factor such as BMP-2. The nucleated cells within the SVF arecounted, and subsequently seeded on a suitable carrier such as calciumphosphate bone substitutes, and implanted for tissue regeneration.Results: After extensive in vitro optimization of the various steps within theconcept, the procedure has been verified in vivo for multiple applications,i.e. regenerative strategies for bone regeneration including spinal fusionand maxillary bone augmentation, articular and intervertebral disccartilage repair, ear and nose reconstructions after burn wounds, andalso for cardiac repair after acute myocardial infarction.Conclusion: The intra-operative procedure is feasible, safe, and showsefficacy in the various animal models, and can be applied in humantrials.

Keywords:

Adipose stem cells , Regenerative medicine , Animal model