Extended Abstract (for invited Faculty only) Stem Cells

3.2.3 - MSCs: Where is the Evidence?

Presentation Topic
Stem Cells
Date
12.04.2022
Lecture Time
15:00 - 15:15
Room
Potsdam 3
Session Type
Special Session
Speaker
  • A. Gobbi (Milano, IT)
Authors
  • A. Gobbi (Milano, IT)
  • K. Herman (Katowice, PL)

Abstract

Introduction

Injury of the knee articular cartilage and osteochondral unit is a significant cause of functional limitation in which the goal of treatment is preservation of the native knee joint. There are a variety of cell-based cartilage and osteochondral unit repair methods that may be used to treat different injuries, given the limited potential for cartilage injury to heal without intervention. Restoration of hyaline-like cartilage is the ultimate goal in treatment of osteochondral unit as it offers an improved durability of repaired tissue and preferable wear characteristics. Over the years many cell-based therapies have been developed to address the need for the long-term viability of repaired tissue. Some of the techniques use mesenchymal stem cells (MSCs) as a core ingredient for tissue repair.

Content

Microfracture, a bone marrow stimulation technique using MSCs, when used wisely and with caution in selected patients has shown good clinical results at short-term follow up. Nonetheless, deterioration of the clinical outcome may be expected after 2 -3 years post-treatment, and degenerative changes are present at long-term follow-up, with a higher rate in older patients with extensive and multiple lesions [1, 2]. Autologous Matrix-Induced Chondrogenesis (AMIC) has emerged as a modification of the microfracture technique by addition of a collagen scaffold. However both of these techniques raise a concern of the damage of the subchondral bone and the formation of microcysts, that may quicken the deterioration of the cartilage and compromise the articular surface for future procedures [3, 4]. Autologous chondrocyte implantation (ACI) consists of a two-step procedure; first, a sample of healthy cartilage is harvested from a non-weight bearing site, followed by an in vitro cell expansion. The second step is the implantation of the chondrocyte suspension into the cartilage defect. Compared to bone marrow stimulating techniques such as microfracture, ACI technique has appeared to be superior over time due to longer-lasting effects, without the concerns of destruction of the subchondral bone [5,6]. However, while techniques using autologous chondrocytes have demonstrated durable cartilage repair, these methods require the patient to undergo two surgical procedures due to the need for chondrocyte culture.

Hyaluronic acid-based scaffold with bone marrow aspirate concentrate (HA-BMAC) was developed 30 years ago, it allowed the treatment of larger cartilage defects in a one-step surgery with biologic tissue such as mesenchymal stem cells, chondrocytes, or platelet-rich plasma. This technique has provided long-term results and has proven its superiority to microfracture due to lasting effect over ten years compared to the 2-3 years with microfracture technique [2]. Moreover, it can be used even in cases of multiple compartment injury, extensive lesions, or in older patients [7-10]. This procedure provides a good source of chondrocytes, whether directly or through differentiation of multipotent precursor cells, capable of producing hyaline-like cartilage, with minimal formation of fibrocartilage tissue [10].

Lately more attention was brought to the osteochondral unit and especially the role of subchondral bone in maintaining homeostasis of the joint [4]. Bone marrow lesions (BMLs) are the focal changes in the subchondral bone and can be identified by magnetic resonance imaging (MRI). A technique using MSCs to treat BMLs, the Osteo-Core-Plasty (Marrow Cellution™) is a minimally invasive subchondral bone augmentation that offers both biologic and structural components to optimize the osteochondral environment for regeneration. This technique may also by applied in treatment of insufficiency fractures, subchondral cysts, and avascular necrosis [11, 12].

MSCs are also found in other sources than bone marrow, one of which is fat tissue. Adipose derived Mesenchymal Stem Cells (ADMSCs) are quickly becoming a viable source of MSC, not only because they are easy to harvest but also have a high concentration of progenitor cells. Primary outcomes of the use of microfragmented adipose tissue (MFAT) injection in elderly patients with knee osteoarthritis (OA) have shown good clinical results compared with the pre-treatment state and could be an alternative treatment for elderly patients 60 years or older [13, 14].

Summarizing, over 30 years of using MSCs have shown good and very good clinical outcomes in treatment of osteochondral unit lesions and OA.

References

References:

1. Gobbi A, Karnatzikos G, Kumar A. Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes. Knee Surg Sports Traumatol Arthrosc. 2014 Sep;22(9):1986–96.

2. Gobbi A, Whyte GP. One-Stage Cartilage Repair Using a Hyaluronic Acid-Based Scaffold With Activated Bone Marrow-Derived Mesenchymal Stem Cells Compared With Microfracture: Five-Year Follow-up. Am J Sports Med. 2016 Nov;44(11):2846–54.

3. Frank RM, Cotter EJ, Nassar I, Cole B. Failure of Bone Marrow Stimulation Techniques. Sports Med Arthrosc Rev. 2017 Mar;25(1):2–9.

4. Gobbi A, Alvarez R, Irlandini E, Dallo I. Current Concepts in Subchondral Bone Pathology. In: Gobbi A, Lane JG, Longo UG, Dallo I, editors. Joint Function Preservation: A Focus on the Osteochondral Unit [Internet]. Cham: Springer International Publishing; 2022

5. Gobbi A, Lane JG, Dallo I. Editorial Commentary: Cartilage Restoration-What Is Currently Available? Arthroscopy. 2020 Jun;36(6):1625–8.

6. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994 Oct 6;331(14):889–95.

7. Gobbi A, Karnatzikos G, Sankineani SR. One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med. 2014 Mar;42(3):648–57.

8. Gobbi A, Karnatzikos G, Scotti C, Mahajan V, Mazzucco L, Grigolo B. One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions: Results at 2-Year Follow-up. Cartilage. 2011 Jul;2(3):286–99.

9. Gobbi A, Scotti C, Karnatzikos G, Mudhigere A, Castro M, Peretti GM. One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years. Knee Surg Sports Traumatol Arthrosc. 2017 Aug;25(8):2494–501.

10. Gobbi A, Whyte GP. Long-term Clinical Outcomes of One-Stage Cartilage Repair in the Knee With Hyaluronic Acid-Based Scaffold Embedded With Mesenchymal Stem Cells Sourced From Bone Marrow Aspirate Concentrate. Am J Sports Med. 2019 Jun;47(7):1621–8.

11. Szwedowski D, Dallo I, Irlandini E, Gobbi A. Osteo-core Plasty: A Minimally Invasive Approach for Subchondral Bone Marrow Lesions of the Knee. Arthrosc Tech. 2020 Nov;9(11):e1773–7

12. Gobbi A, Dallo I. Osteo-Core-Plasty technique for the treatment of a proximal tibial subchondral cystic lesion. 2021;

13. Dallo I, Morales M, Gobbi A. Platelets and Adipose Stroma Combined for the Treatment of the Arthritic Knee. Arthroscopy Techniques. 2021 Oct 6;10.

14. Gobbi A, Dallo I, Rogers C, Striano RD, Mautner K, Bowers R, et al. Two-year clinical outcomes of autologous microfragmented adipose tissue in elderly patients with knee osteoarthritis: a multi-centric, international study. Int Orthop. 2021 May;45(5):1179–88.

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