Safety and Complications Reporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique

Centeno, Christopher J.; Schultz, John R.; Cheever, Michelle; Robinson, B.S.; Freeman, Michael; Marasco, Wayne A.

doi:10.2174/157488810790442796

Cited by 144 publications

(115 citation statements)

References 22 publications

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“…In addition, our data clearly demonstrate a durable effect of single injection of adipose-derived SVF cells. Similar finding was documented previously with bone marrow-derived cultured MSCs therapy in patients with osteoarthritis [11]. In this study, there were 67.8% of patients with knee OA candidates for total knee arthroplasty and 6.9% reported that they opted for knee replacement in a median follow-up of 435 days [11].…”

Section: Discussionsupporting

confidence: 88%

“…Reduction of pain as well as meniscal volume increase was noticed in MSC-treated patients but not in placebo control group [17]. Despite using different cell sources, both studies [11,17] are in accordance with our findings regarding safety and clinical effect of cell therapies in similar orthopedic indications.…”

Section: Discussionsupporting

confidence: 88%

“…It demonstrated safety and clinical efficacy in most patients treated. In a subgroup of 133 patients with knee OA 50% score improvement was noticed in 63.2% cases at an average reporting time of 11.3 months from the first cell application [11]. Vangsness et al reported results of a randomized, double-blind, controlled study in 55 patients with knee OA and partial medial meniscectomy treated with allogeneic bone marrow-derived MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Not surprisingly, most patients were treated for knee and/or hip OA and our treatment strategy allowed multiple joint treatments during one surgical procedure. Based on previous studies demonstrating migratory capability of MSCs [8][9][10][11][12] we allowed intraarticular or periarticular (synovial stroma or loose connective tissue immediately adjacent to the joint cartilage) application of SVF cells. We hypothesized that stem cells as well as other regenerative stromal cells may contribute to the cartilage healing process via two mechanisms: 1) paracrine effect and 2) cell migration, differentiation and proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…Preclinical animal studies that utilize MSCs demonstrated safety and efficacy in treatment of OA, cartilage defects or other orthopedic conditions [7][8][9][10]. In humans, the largest collection of culture-expanded bone marrow-derived MSCs used for treatment of 339 patients with OA was recently documented and more than 75% improvement was reported in 41.4% and more than 50% improvement was reported in 63.2% of patients [11]. No severe side effects and no neoplastic complications were detected at any stem cell re-implantation site in a mean follow-up 435 days [11].…”

Section: Introductionmentioning

confidence: 99%

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Stromal Vascular Fraction Cells of Adipose and Connective Tissue in People with Osteoarthritis: A Case Control Prospective Multi-Centric Non-Randomized Study

Moster¹,

Lukác²,

Proefrock³

et al. 2017

Glob Surg

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Objective: Stromal vascular fraction (SVF), containing high amount of stem cells and other regenerative cells, can be easily obtained from loose connective tissue that is associated with adipose tissue. Here we evaluated safety and clinical efficacy of freshly isolated autologous SVF cells in a case control prospective multi-centric non-randomized study in patients with grade 2-4 degenerative osteoarthritis. Methods:A total of 1128 patients underwent standard liposuction under local anesthesia and SVF cells were isolated and prepared for application into 1-4 large joints. A total of 1856 joints, mainly knee and hip joints, were treated with a single dose of SVF cells. 1114 patients were followed for 12.1-54.3 months (median 17.2 months) for safety and efficacy. Modified KOOS/HOOS Clinical Score was used to evaluate clinical effect and was based on pain, non-steroid analgesic usage, limping, extent of joint movement, and joint stiffness evaluation before and at 3,6 and 12 months after the treatment. Results:No serious side effects, systemic infection or cancer was associated with SVF cell therapy. Most patients gradually improved 3-12 months after the treatment. At least 75% Score improvement was noticed in 63% of patients and at least 50% Score improvement was documented in 91% of patients 12 months after SVF cell therapy. Obesity and higher grade of OA were associated with slower healing. Conclusion:Here we report a novel and promising treatment approach for patients with degenerative osteoarthritis that is safe, cost-effective, and relying only on autologous cells.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stromal Vascular Fraction Cells of Adipose and Connective Tissue in People with Osteoarthritis: A Case Control Prospective Multi-Centric Non-Randomized Study

Moster¹,

Lukác²,

Proefrock³

et al. 2017

Glob Surg

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Mesenchymal stem cells expanded in human platelet lysate display a decreased inhibitory capacity on T‐ and NK‐cell proliferation and function

et al. 2011

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The use of fetal bovine serum (FBS) for the culture and expansion of mesenchymal stromal cells (MSCs) limits their possible clinical applications. Although some recent studies recommended substituting FBS with human platelet lysate (HPL) for the expansion of MSCs for clinical use, the functional capacity of the expanded cells has only been partially explored. 10% FBS and two other commercial FBS-containing media (MesenCult and MesenPro) were compared with 10% HPL-containing medium for their ability to support MSCs expansion and immunomodulation. We demonstrate that HPL sustained MSC proliferation and expansion in vitro. However, the cumulative cell numbers recovered were comparable with those obtained in MesenPro medium. Moreover, we show that HPL alters the expression of some relevant MSC surface molecules, namely the DNAM-1 ligands PVR and Nectin-2, the NKG2D ligand ULBP3, the adhesion molecules CD49d and avb3 and the fibroblast-associated protein. In addition, MSCs cultured in HPL displayed impaired inhibitory capacity on T-cell proliferation to alloantigen and NK-cell proliferation and cytotoxicity. Finally, they showed decreased constitutive PGE2 production while IL-6, IL-8 and RANTES secretion were upregulated. These results imply some limitations in the use of HPL for the expansion of MSCs to be used as immunomodulators in clinical applications.Key words: Graft-versus-host disease . Hematopoietic stem cell transplantation . Human platelet lysate . Mesenchymal stromal cells . NK cells IntroductionHuman mesenchymal stromal cells (MSCs) have attracted major attention for their possible clinical use [1]. In addition to their tissue regenerative capacity, they have immune-modulatory properties for which they are used in the prophylaxis and treatment of GVH disease (GVHD) [2]. MSCs have been shown to prevent graft failure and to promote engraftment in hematopoietic stem cell transplantation (HSCT) [1,2]. The expansion of MSCs for their clinical use has been done under different culture conditions, most of which were based on the addition of fetal bovine serum (FBS) as a supplement for different media [3]. Under these culture conditions, anti-FBS antibodies have been detected in most patients infused with MSCs cultured in the presence of FBS [4]. The identification of suitable culture conditions for optimal expansion and appropriate functional capability of MSCs still remains a crucial matter [5].The recent interest in obtaining high numbers of MSCs for clinical use has led to the development of therapeutic protocols based on the non-transfusional use of hemocomponents such as Little is known about the effect of HPL-conditioned media on the functional properties of MSCs and hence on their efficacy in clinical application. Notably, HPL contains numerous bioactive molecules stored within the platelet organelles including adhesion molecules, coagulation factors, protease inhibitors and proteoglycans [8], as well as growth factors. These include platelet-derived growth factor (PDGF), basic fibroblast-derived growth ...

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Regeneration of articular cartilage using adipose stem cells

2016

J Biomedical Materials Res

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Articular cartilage (AC) has limited potential for self-regeneration and damage to AC eventually leads to the development and progression of osteoarthritis (OA). Cell implantation strategies have emerged as a new treatment modality to regenerate AC. Adipose stem cells/adipose-derived stromal cells (ASCs) have gained attention due to their abundance, excellent proliferative potential, and minimal morbidity during harvest. These advantages lower the cost of cell therapy by circumventing time-consuming procedure of culture expansion. ASCs have drawn attention as a potential source for cartilage regeneration since the feasibility of chondrogenesis from ASCs was first reported. After several groups reported inferior chondrogenesis from ASCs, numerous methods were devised to overcome the intrinsic properties. Most in vivo animal studies have reported good results using predifferentiated or undifferentiated, autologous or allogeneic ASCs to regenerate cartilage in osteochondral defects or surgically-induced OA. In this review, we summarize literature on the isolation and in vitro differentiation processes of ASCs, in vivo studies to regenerate AC in osteochondral defects and OA using ASCs, and clinical applications of ASCs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1830-1844, 2016.

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Safety and Complications Reporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique

Cited by 144 publications

References 22 publications

Stromal Vascular Fraction Cells of Adipose and Connective Tissue in People with Osteoarthritis: A Case Control Prospective Multi-Centric Non-Randomized Study

Stromal Vascular Fraction Cells of Adipose and Connective Tissue in People with Osteoarthritis: A Case Control Prospective Multi-Centric Non-Randomized Study

Mesenchymal stem cells expanded in human platelet lysate display a decreased inhibitory capacity on T‐ and NK‐cell proliferation and function

Regeneration of articular cartilage using adipose stem cells

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