Evaluation of the therapeutic potential of infrapatellar fat pad adipose-derived stem cells and their secretome for regenerating knee articular cartilage in a rat model of osteoarthritis

Abstract

Background: Mesenchymal stem cell (MSC) therapy has ameliorative effects for treating knee osteoarthritis (KOA) disease. Moreover, there is a growing interest in using MSCs-derived secretome (Sec) containing trophic factors secreted by MSCs for KOA treatment. Recently, some studies have suggested that the combination of MSCs and Sec has the potential to treat the diseases.

Aims: This study aimed to evaluate the ameliorative effects of combined administration of infrapatellar fat pad (IPFP)-derived MSCs, a type of adipose-derived stem cells (ASCs), for treating degenerated cartilage in a rat model of KOA.

Methods: IPFP-ASCs were isolated from the IPFP of male rats. Sec was obtained from IPFP-ASCs in the fourth passage. Eight weeks after the induction of KOA by collagenase II, the rats were divided into 5 groups (n=5), including a control group with no treatment, and four experimental groups that received sodium hyaluronate (Hyalgan^®, Hya), ASCs, Sec, and IPFP-ASCs+Sec, respectively by an infrapatellar injection. To perform the pathological and radiological evaluations, the animals were sacrificed 8 weeks later.

Results: Our findings indicated that combined administration of the IPFP-ASCs and Sec statistically (P<0.05) improved scores of medial tibial and femoral condyles and medial fabella osteophytes. Also, it statistically (P<0.05) enhances the cartilage surface, matrix, cell distribution and population viability, and subchondral bone indices. No statistical difference was observed between IPFP-ASCs+Sec and IPFP-ASCs.

Conclusion: Administration of IPFP-ASCs+Sec has a therapeutic potential to treat KOA in rats. However, there is no difference in the combined administration of IPFP-ASCs and Sec with IPFP-ASCs alone.

Keywords: Adipose-derived stem cells; Articular cartilage; Infrapatellar fat pad; Osteoarthritis; Secretome.

Fig. 1

Flow cytometry study findings indicated that IPFP-ASCs were negative for hematopoietic markers CD34 and CD45 and positive for MSC markers, CD44 and CD90

Fig. 2

AP and LT view of knee joints 8 weeks after treatment in KOA-induced rats

Fig. 3

Radiological scores of knee joints in the different groups. IPFP-ASCs+Sec: Infrapatellar fat pad adipose-derived stem cells+Secretome, IPFP-ASCs: Infrapatellar fat pad adipose-derived stem cells, Sec: Secretome, and Hya: Hyalgan^®. Data are shown as mean±SD (n=5). ^* P<0.05, ^** P<0.01, ^*** P<0.001, and ^**** P<0.0001, respectively

Fig. 4

H&E-stained sections from the surface of articular cartilage of all groups. IPFP-ASCs+Sec: Infrapatellar fat pad adipose-derived stem cells+Secretome, IPFP-ASCs: Infrapatellar fat pad adipose-derived stem cells, Sec: Secretome, and Hya: Hyalgan^®. Severely irregular articular surfaces comprise the mostly fibrous cartilaginous matrix (control). Mild articular surface irregularity with hyaline cartilage matrix foci (Hya). Cluster cell distribution and a mixture of the hyaline-fibrous matrix (IPFP-ASCs). A mixture of cylindrical-cluster arrangement of chondrocytes with moderate irregularity of articular surface (Sec). Smooth continuous articular surface with the cylindrical distribution of chondrocytes (IPFP-ASCs+Sec)

Fig. 5

Histological scores of KOA in rat models. IPFP-ASCs+Sec: Infrapatellar fat pad adipose-derived stem cells+Secretome, IPFP-ASCs: Infrapatellar fat pad adipose-derived stem cells, Sec: Secretome, and Hya: Hyalgan^®. Data are shown as mean±SD (n=5). ^* P<0.05 and ^** P<0.01, respectively