Cells don't lie...
Am J Sports Med. 2023 Sep;51(11):3008-3024.
doi: 10.1177/03635465231187042. Epub 2023 Aug 2.
Donor-Matched Peripheral Blood-Derived Mesenchymal Stem Cells Combined With Platelet-Rich Plasma Synergistically Ameliorate Surgery-Induced Osteoarthritis in Rabbits: An In Vitro and In Vivo Study
Kaibo Zhang 1,
Tianhao Xu 1,
Huiqi Xie 2,
Jian Li 1,
Weili Fu 1
Affiliations expand
Abstract
Background: Osteoarthritis (OA) is a common disease that causes joint pain and disability. Stem cell therapy is emerging as a promising treatment for OA.
Purpose: To evaluate the ability of peripheral blood-derived mesenchymal stem cells (PBMSCs) combined with donor-matched platelet-rich plasma (PRP) to treat OA in a rabbit model.
Study design: Controlled laboratory study.
Methods: PBMSCs and donor-matched PRP were isolated and prepared from the same rabbit. PBMSCs were treated with serum-free medium, fetal bovine serum, and PRP; a series of PBMSC behaviors, including proliferation, migration, and adhesion, were compared among groups. The ability of PBMSCs or PRP alone and PBMSCs+PRP to protect chondrocytes against proinflammatory cytokine (interleukin 1β [IL-1β]) treatment was compared by analyzing reactive oxygen species (ROS)-scavenging ability and apoptosis. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate the expression of extracellular matrix (ECM) metabolism genes and proteins, and Western blotting was used to explore the potential mechanism of the corresponding signaling pathway. In vivo, the effect of PBMSCs+PRP on cartilage and inflammation of the synovium was observed in a surgery-induced OA rabbit model via gross observation, histological and immunohistochemical staining, and enzyme-linked immunosorbent assay.
Results: Proliferation, migration, and adhesion ability were enhanced in PBMSCs treated with PRP. Moreover, compared with either PBMSCs or PRP alone, PBMSCs+PRP enhanced ROS-scavenging ability and inhibited apoptosis in IL-1β-treated chondrocytes. PBMSCs+PRP also reversed the IL-1β-induced degradation of collagen type 2 and aggrecan and increased expression of matrix metalloproteinase 13, and this effect was related to increased expression of ECM synthesis and decreased expression of degradation and inflammatory genes and proteins. Mechanistically, PBMSCs+PRP reduced the phosphorylation of inhibitor of nuclear factor-κBα (IκBα), which further inhibited the phosphorylation of downstream nuclear factor-κB (NF-κB) in the NF-κB signaling pathway. In vivo, compared with PBMSCs or PRP alone, intra-articular (IA) injection of PBMSCs+PRP enhanced cartilage regeneration and attenuated synovial inflammation in OA-induced rabbits.
Conclusion: These results demonstrate that PRP could enhance biological activities, including viability, migration, and adhesion, in PBMSCs. PBMSCs+PRP could rescue ECM degeneration by inhibiting inflammatory signaling in IL-1β-treated OA chondrocytes. In addition, IA injection of PBMSCs+PRP effectively attenuated OA progression in a surgery-induced OA rabbit model.
Clinical relevance: PBMSCs+PRP may provide a promising treatment for knee OA, and this study can advance the related basic research.
Keywords: chondrocytes; osteoarthritis; peripheral blood mesenchymal stem cells; platelet-rich plasma.
Tissue Cell. 2023 Aug;83:102144.
doi: 10.1016/j.tice.2023.102144. Epub 2023 Jun 20.
Periosteum-derived skeletal stem cells encapsulated in platelet-rich plasma enhance the repair of bone defect
Haibo Dai 1,
Haici Zhang 1,
Zhilong Qiu 1,
Qiang Shi 2
Affiliations expand
Free article
Abstract
Background: Spontaneous restoration of large bone defects remains a challenge under infections, tumors, and crushing conditions. Current stem cell-based therapies for treating bone defects need improvement, because the used stem cells are isolated by a traditional protocol, which is based on their properties of in-vitro plastic adherence and fibroblastic colony formation. The stem cells isolated by the traditional protocol belong to a multicellular type mixture, individual cells vary in proliferative and osteogenic potential. Thus, developing a protocol capable of isolating stem cell subset with higher purity is required and urgent.
Aim: This study aimed to sort a subpopulation of stem cells from periosteum using flow cytometry (named as FC-PSCs), and evaluate the proliferative and osteogenic capacity of FC-PSCs in-vitro, and then establish a new stem cell-based therapies for treating bone defects by delivering the FC-PSCs within platelet-rich plasma (PRP).
Methods: Mouse periosteum was used to sort FC-PSCs using flow cytometry with CD45-TER119-TIE2-ITGAV+CD90 + 6C3-CD105- markers, or isolate periosteum-derived stem cells with the traditional protocol (TP-PSCs) as control. After evaluating the FC-PSCs proliferation and osteogenic differentiation in-vitro as well as the promotive efficacy of platelet-rich plasma (PRP) on FC-PSCs proliferation and osteogenic differentiation, the FC-PSCs were delivered into the femoral epiphysis bone defect site of a mouse model by platelet-rich plasma (PRP). At postoperative 14 or 28 days, these mice were euthanized for harvest the femur specimens for micro-CT, histological evaluation.
Results: In-vitro results determined that the FC-PSCs showed more capacity for proliferation and osteogenic differentiation compared with the TP-PSCs. In addition, in-vitro results showed the promotive efficacy of PRP on FC-PSCs proliferation and osteogenic differentiation. In-vivo results showed that the FC-PSCs delivered by PRP was able to facilitate the repair of bone defects by stimulating new bone formation and remodeling.
Conclusion: FC-PSCs delivered by PRP enhance the repair of bone defects by stimulating new bone formation and remodeling.
Keywords: Bone defect; Periosteum; Platelet-rich plasma; Skeletal stem cells.
Pathol Res Pract. 2023 Aug;248:154575.
doi: 10.1016/j.prp.2023.154575. Epub 2023 May 26.
Supporting wound healing by mesenchymal stem cells (MSCs) therapy in combination with scaffold, hydrogel, and matrix; State of the art
Bayu Indra Sukmana 1,
Ria Margiana 2,
Yasir Qasim Almajidi 3,
Sami G Almalki 4,
Ahmed Hjazi 5,
Sana Shahab 6,
Rosario Mireya Romero-Parra 7,
Adeeb Abdulally Abdulhussien Alazbjee 8,
Afa Alkhayyat 9,
Vivek John 10
Affiliations expand
Abstract
Non-healing wounds impose a huge annual cost on the survival of different countries and large populations in the world. Wound healing is a complex and multi-step process, the speed and quality of which can be changed by various factors. To promote wound healing, compounds such as platelet-rich plasma, growth factors, platelet lysate, scaffolds, matrix, hydrogel, and cell therapy, in particular, with mesenchymal stem cells (MSCs) are suggested. Nowadays, the use of MSCs has attracted a lot of attention. These cells can induce their effect by direct effect and secretion of exosomes. On the other hand, scaffolds, matrix, and hydrogels provide suitable conditions for wound healing and the growth, proliferation, differentiation, and secretion of cells. In addition to generating suitable conditions for wound healing, the combination of biomaterials and MSCs increases the function of these cells at the site of injury by favoring their survival, proliferation, differentiation, and paracrine activity. In addition, other compounds such as glycol, sodium alginate/collagen hydrogel, chitosan, peptide, timolol, and poly(vinyl) alcohol can be used along with these treatments to increase the effectiveness of treatments in wound healing. In this review article, we take a glimpse into the merging scaffolds, hydrogels, and matrix application with MSCs therapy to favor wound healing.
Keywords: Cell therapy; Hydrogel; Matrix; Mesenchymal stem cells (MSCs); Scaffold; Wound healing.
