Abstract
Human adipose mesenchymal stem/stromal cells (Ad-MSCs) have been proposed as a suitable option for bone tissue engineering. However, donor age, weight, and gender might affect the outcome. There is still a lack of knowledge of the effects the donor tissue site might have on Ad-MSCs function. Thus, this study investigated proliferation, stem cell, and osteogenic differentiation capacity of human Ad-MSCs obtained from subcutaneous fat tissue acquired from different locations (abdomen, hip, thigh, knee, and limb). Ad-MSCs from limb and knee showed strong proliferation despite the presence of osteogenic stimuli, resulting in limited osteogenic characteristics. The less proliferative Ad-MSCs from hip and thigh showed the highest alkaline phosphatase (AP) activity and matrix mineralization. Ad-MSCs from the abdomen showed good proliferation and osteogenic characteristics. Interestingly, the observed differences were not dependent on donor age, weight, or gender, but correlated with the expression of Sox2, Lin28A, Oct4α, and Nanog. Especially, low basal Sox2 levels seemed to be pivotal for osteogenic differentiation. Our data clearly show that the donor tissue site affects the proliferation and osteogenic differentiation of Ad-MSCs significantly. Thus, for bone tissue engineering, the donor site of the adipose tissue from which the Ad-MSCs are derived should be adapted depending on the requirements, e.g., cell number and differentiation state.
Highlights
The regeneration of large bone defects after a trauma or tumor surgery is still a major issue in orthopedic surgery [1]
The Proliferation of adipose mesenchymal stem/stromal cells (Ad-mesenchymal stem/stromal cells (MSCs)) Varies Depending on the Donor Site
No significant differences were found in the number of Ad-MSCs obtained after collagenase digestion of fat tissues derived from different donor sites
Summary
The regeneration of large bone defects after a trauma or tumor surgery is still a major issue in orthopedic surgery [1]. Specialized surgical techniques have been deployed in order to reconstitute large bone defects, ranging from microvascular anastomosed autogenous bone grafting (fibula transfer flap) to Masquelet technique with Ilizarov external fixation and bone segmental transport. These methods require large amounts of bony tissue to fill the defects and provide mesenchymal stem/stromal cells (MSCs), which are essential to induce bone healing [3,4]. The most frequently used autologous bone grafting requires additional surgical intervention. This carries the risk of infection as well as morbidity at the donor site [5]. Allogeneic bone tissue, which might serve as an alternative, can cause immunological reactions [6]
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