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{{Short description|Medical treatment for articular cargilage damage}}
{{refimprove|date=July 2015}}
{{Expert-subject|medicine|date=November 2008}}
{{Multiple issues|{{UDP|date=September 2017}}
{{more citations needed|date=July 2015}}}}

{{Infobox medical intervention
'''Autologous chondrocyte implantation''' ('''ACI''', [[ATC code]] {{ATC|M09|AX02}}) is a biomedical treatment that repairs damages in articular cartilage. ACI provides pain relief while at the same time slowing down the progression or considerably delaying partial or total [[joint replacement]] ([[knee replacement]]) surgery. The goal of ACI is to allow people suffering from [[articular cartilage damage]] to return to their old lifestyle; regaining mobility, going back to work and even practicing sports again.
| name = Autologous chondrocyte implantation
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| image =Autologous Chondrocyte Implantation (ACI) Therapy.png
| caption =Autologous Chondrocyte Implantation
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| specialty = orthopedia
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'''Autologous chondrocyte implantation''' ('''ACI''', [[ATC code]] {{ATC|M09|AX02}}) is a biomedical treatment that repairs damages in articular cartilage. ACI provides pain relief while at the same time slowing down the progression or considerably delaying partial or total [[joint replacement]] ([[knee replacement]]) surgery.


ACI procedures aim to provide complete [[hyaline]] repair tissues for [[articular cartilage repair]]. Over the last 20 years, the procedure has become more widespread and it is currently probably the most developed articular cartilage repair technique.
ACI procedures aim to provide complete [[hyaline]] repair tissues for [[articular cartilage repair]]. Over the last 20 years, the procedure has become more widespread and it is currently probably the most developed articular cartilage repair technique.


The procedure fails in about 15% of people.<ref>{{cite journal|last1=Andriolo|first1=L|last2=Merli|first2=G|last3=Filardo|first3=G|last4=Marcacci|first4=M|last5=Kon|first5=E|title=Failure of Autologous Chondrocyte Implantation.|journal=Sports Medicine and Arthroscopy Review|date=March 2017|volume=25|issue=1|pages=10–18|doi=10.1097/JSA.0000000000000137|pmid=28045868|s2cid=19085219}}</ref>
The surgical technique was first performed in Sweden in 1987; the results of the 9 year follow up are available in [[Lars Peterson]] et al. 2000. Brittberg published the first description of the technique on humans in 1994. He reported good and promising results with 23 patients for defects on the femoral condyles (Brittberg et al., 1994).The technique also seems promising with regard to long-term results.<ref>
{{cite journal |author=Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L |title=Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation |journal=N. Engl. J. Med. |volume=331 |issue=14 |pages=889–95 |date=October 1994 |pmid=8078550 |doi=10.1056/NEJM199410063311401}}</ref>


__TOC__
==Procedure==
This cell based [[articular cartilage repair]] procedure takes place in three stages. In a first stage, between 200 and 300 milligrams [[cartilage]] is sampled arthroscopically from a less [[weight bearing]] area from either the intercondylar notch or the superior ridge of the medial or lateral femoral condyle of the patient. The matrix is removed enzymatically and the chondrocytes isolated. These cells are grown in vitro in a specialised laboratory for approximately four to six weeks, until there are enough cells to reimplant on the damaged area of the articular cartilage. The patient then undergoes a second treatment, in which the chondrocytes are applied on the damaged area during an open-knee surgery (also called arthrotomy). These autologous cells should adapt themselves to their new environment by forming new [[cartilage]]. During the implantation, [[chondrocyte]]s are applied on the damaged area in combination with a membrane (tibial periosteum or biomembrane) or pre-seeded in a scaffold matrix.


== ACI Complications ==
== Complications ==
The occurrence of subsequent surgical procedures (SSPs), primarily arthroscopy, following ACI is common. For example, in the Study of the Treatment of Articular Repair (STAR), 49% of Carticel ACI patients underwent an SSP on the treated knee, during the 4-year follow up. The most common serious adverse events (up to 5% of patients), include arthrofibrosis and joint adhesions, graft overgrowth, chondromalacia or chondrosis, cartilage injury, graft complication, meniscal lesion, graft delamination, and osteoarthritis. Source: Carticel.
The occurrence of subsequent surgical procedures (SSPs), primarily arthroscopy, following ACI is common. For example, in the Study of the Treatment of Articular Repair (STAR), 49% of Carticel ACI patients underwent an SSP on the treated knee, during the 4-year follow up. The most common serious adverse events (up to 5% of patients), include [[arthrofibrosis]] and joint adhesions, graft overgrowth, [[chondromalacia]] or [[Chondromalacia patellae|chondrosis]], cartilage injury, graft complication, meniscal lesion, graft delamination, and osteoarthritis.<ref>Source: Carticel.</ref>


A recent study from Germany, published in November 2008 issue of the American Journal of Sports Medicine, analyzed 349 ACI procedures of the knee joint. Three different ACI techniques were used. A major proportion of complications after ACI can be summarized by 4 major diagnoses: symptomatic hypertrophy, disturbed fusion, delamination, and graft failure. Among those, the overall complication rate and incidence of hypertrophy of the transplant were higher for periosteum-covered ACI. Furthermore, an increased rate of symptomatic hypertrophy was found for patellar defects. Source: Philipp Niemeyer, MD, et al.: Characteristic Complications After Autologous Chondrocyte Implantation for Cartilage Defects of the Knee Joint. The American Journal of Sports Medicine 36:2091-2099 (2008).
A recent study from Germany, published in the November 2008 issue of the American Journal of Sports Medicine, analyzed 349 ACI procedures of the knee joint. Three different ACI techniques were used. A major proportion of complications after ACI can be summarized by 4 major diagnoses: symptomatic hypertrophy, disturbed fusion, delamination, and graft failure. Among those, the overall complication rate and incidence of hypertrophy of the transplant were higher for periosteum-covered ACI. Furthermore, an increased rate of symptomatic hypertrophy was found for patellar defects.<ref>Source: Philipp Niemeyer, MD, et al.: "Characteristic Complications After Autologous Chondrocyte Implantation for Cartilage Defects of the Knee Joint". ''The American Journal of Sports Medicine'' 36:2091–2099 (2008).</ref>


== Improvement of ACI ==
==Randomized clinical studies==
Knutsen and coworkers have published the 2-year<ref>{{cite journal |author=Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grøntvedt T, [[Eirik Solheim|Solheim E]], Strand T, Roberts S, Isaksen V, Johansen O|title=Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial |journal=J Bone Joint Surg Am |volume=86-A |issue=3 |pages=455–64 |date=March 2004 |pmid=14996869 |url=http://www.ejbjs.org/cgi/pmidlookup?view=long&pmid=14996869}}</ref> and 5-year<ref>{{cite journal |author=Knutsen G, Drogset JO, Engebretsen L |title=A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years |journal=J Bone Joint Surg Am |volume=89 |issue=10 |pages=2105–12 |date=October 2007 |pmid=17908884 |doi=10.2106/JBJS.G.00003 |url=http://www.ejbjs.org/cgi/pmidlookup?view=long&pmid=17908884|display-authors=etal}}</ref> follow-up results after surgery in patients randomized for ACI or [[microfracture surgery|microfracture]] treatment of localized articular defects of the knee joint. At the two-year follow-up the authors concluded that: "Both methods had acceptable short-term clinical results. There was no significant difference in macroscopic or histological results between the two treatment groups and no association between the histological findings and the clinical outcome at the two-year time-point." At the five-year follow-up the conclusions were similar: "Both methods provided satisfactory results in 77% of the patients at five years. There was no significant difference in the clinical and radiographic results between the two treatment groups and no correlation between the histological findings and the clinical outcome. One-third of the patients had early radiographic signs of osteoarthritis five years after the surgery. Further long-term follow-up is needed to determine if one method is better than the other and to study the progression of osteoarthritis."


Techniques such as the EELS-TALC<ref>{{cite web |title=EELS-TALC |url=https://www.ncrm.org/myth/eelstalc/ |website=EELS-TALC |access-date=20 March 2021}}</ref> to enhance ACI and its next generation advancement called Matrix Assisted Chondrocyte Implantation (MACI)<ref>{{cite journal |last1=Jacobi |first1=M |title=MACI - a new era? |journal=Sports Med Arthrosc Rehabil Ther Technol |date=2011 |volume=3 |issue=1 |page=10 |doi=10.1186/1758-2555-3-10 |pmid=21599919 |pmc=3117745 |doi-access=free }}</ref> with enabling chondrocytes to be tissue engineered with long term native knee cartilage phenotype maintenance in vitro and in vivo,<ref>{{cite journal |last1=Yasuda |first1=Ayuko |title=In vitro culture of chondrocytes in a novel thermoreversible gelation polymer scaffold containing growth factors |journal=Tissue Engineering |date=2006 |volume=12 |issue=5 |pages=1237–1245 |doi=10.1089/ten.2006.12.1237 |pmid=16771637 |url=https://doi.org/10.1089/ten.2006.12.1237}}</ref><ref>{{cite journal |last1=Arumugam |first1=S |title=Transplantation of autologous chondrocytes ex-vivo expanded using Thermoreversible Gelation Polymer in a rabbit model of articular cartilage defect |journal=Journal of Orthopedics |date=2007 |volume=14 |issue=2 |pages=223–225 |doi=10.1016/j.jor.2017.01.003 |pmid=28203047 |pmc=5293721 }}</ref> with the engineered tissue construct containing stem cell progenitors<ref>{{cite journal |last1=Katoh |first1=Shojiro |title=A three-dimensional in vitro culture environment of a novel polymer scaffold, yielding chondroprogenitors and mesenchymal stem cells in human chondrocytes derived from osteoarthritis-affected cartilage tissue |journal=Journal of Orthopedics |date=2021 |volume=23 |pages=138–141 |doi=10.1016/j.jor.2021.01.005|issn=0972-978X |pmid=33510554 |pmc=7815488 |doi-access=free }}</ref> along with those expressing pluripotency markers<ref>{{cite journal |last1=Katoh |first1=Shojiro |title=Articular chondrocytes from osteoarthritic knee joints of elderly, in vitro expanded in thermo-reversible gelation polymer (TGP), exhibiting higher UEA-1 expression in lectin microarray |journal=Regenerative Therapy |date=2020 |volume=14 |pages=234–237 |doi=10.1016/j.reth.2020.03.006 |pmid=32435676 |pmc=7229400 |doi-access=free }}</ref> and with added advantage of enriched [[hyaluronic acid]] (HA) expression<ref>{{cite journal |last1=Katoh |first1=Shojiro |title=Enhanced expression of hyaluronic acid in osteoarthritis-affected knee-cartilage chondrocytes during three-dimensional in vitro culture in a hyaluronic-acid-retaining polymer scaffold |journal=The Knee |date=2021 |volume=29 |pages=365–373 |doi=10.1016/j.knee.2021.02.019 |pmid=33690017 |doi-access=free }}</ref> by the cells have been reported which will contribute to improved regenerative therapies for cartilage damage.
Saris et al. studied histologic results and clinical outcome in a similar randomized study and concluded that: "One year after treatment, characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture. Short-term clinical outcome was similar for both treatments. The superior structural outcome
may result in improved long-term clinical benefit with characterized chondrocyte implantation. Long-term follow-up is needed to confirm these findings."<ref>{{cite journal |author=Saris DB, Vanlauwe J, Victor J |title=Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture |journal=Am J Sports Med |volume=36 |issue=2 |pages=235–46 |date=February 2008 |pmid=18202295 |doi=10.1177/0363546507311095 |url=http://ajs.sagepub.com/cgi/pmidlookup?view=long&pmid=18202295|display-authors=etal}}</ref>

At present it seems fair to conclude that the repair tissue formed by ACI is as good or possible slightly better than a less invasive and simpler surgical technique 1–2 years after the surgery. ACI has not yet been shown to give better clinical outcome than microfracture at short-term or medium-term follow-up.

Minas et al. studied clinical outcome in a cohort study of 321 patients. They found that defects treated by ACI, which had a prior treatment with marrow stimulating techniques, such as microfracture, were three times more likely to fail than for defects treated by ACI, which did not have a prior marrow stimulating technique. They concluded that marrow stimulating techniques should be employed judiciously in larger cartilage defects that may require future treatment with ACI.<ref>{{cite journal |author=Minas T, Gomoll AH, Rosenberger R, Royce RO, Bryant T |title=Increased failure rate of autologous chondrocyte implantation after previous treatment with marrow stimulation techniques |journal=Am J Sports Med |volume=37 |issue=5 |pages=902–8 |date=May 2009 |pmid=19261905 |doi=10.1177/0363546508330137 |url=http://ajs.sagepub.com/cgi/pmidlookup?view=long&pmid=19261905}}</ref>


== References ==
== References ==
{{Reflist|2}}
{{reflist}}

==External links==
*{{cite journal |author=Hangody L, Füles P |title=Autologous osteochondral mosaicplasty for the treatment of full-thickness defects of weight-bearing joints: ten years of experimental and clinical experience |journal=J Bone Joint Surg Am |volume=85-A |issue=Suppl 2|pages=25–32 |year=2003 |pmid=12721342 |url=http://www.ejbjs.org/cgi/pmidlookup?view=long&pmid=12721342}}
*{{cite journal |author=Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A |title=Two- to 9-year outcome after autologous chondrocyte transplantation of the knee |journal=Clin. Orthop. Relat. Res. |issue=374 |pages=212–34 |date=May 2000 |pmid=10818982 |doi=10.1097/00003086-200005000-00020}}
*{{cite journal |author=Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG |title=Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up |journal=Arthroscopy |volume=19 |issue=5 |pages=477–84 |year=2003 |pmid=12724676 |doi=10.1053/jars.2003.50112 |url=http://linkinghub.elsevier.com/retrieve/pii/S0749806303001245}}
*{{cite journal |author=Hambly K, Bobic V, Wondrasch B, Van Assche D, Marlovits S |date=June 2006 |title=Autologous Chondrocyte Implantation Postoperative Care and Rehabilitation |journal=The American Journal of Sports Medicine |volume=34 |issue=6 |pages=1020–38 |pmid=16436540 |doi=10.1177/0363546505281918 |url=http://ajs.sagepub.com/content/34/6/1020.full }}
*{{cite web |title=Autologous Chondrocyte Implantation |year=2002 |format=PDF |publisher=Department of Labor and Industries Office of the Medical Director Technology Assessment |url=http://www.lni.wa.gov/ClaimsIns/Files/OMD/AciUpdate.pdf}}
*{{cite web |title=Cartilage Transplantation |publisher=University of South Alabama Human Performance and Joint Restoration Center. USA Department of Orthopaedics |url=http://www.southalabama.edu/usahealthsystem/jointrestoration/cartilage.html}}
*{{cite web |author=Minas, Tom |title=Autologous chondrocyte implantation for full thickness cartilage defects of the knee |publisher=Brigham and Women’s Hospital, Cartilage Repair Center |url=http://www.cartilagerepaircenter.org}}
*“Minimally Invasive Total Knee Replacement.” [http://orthoinfo.aaos.org American Academy of Orthopaedic Surgeons.] February 2005.
* [http://news.bbc.co.uk/1/hi/health/1556883.stm BBC Coverage of Autologous Chondrocyte graft in UK]
* [http://www.action.org.uk/touching_lives/pdfs/touching_lives.2003.autumn.pdf UK Health Charity covers Autologous Chondrocyte grafts]


{{Bone, cartilage, and joint procedures}}
{{Bone, cartilage, and joint procedures}}
{{Other drugs for disorders of the musculo-skeletal system}}


[[Category:Orthopedic surgical procedures]]
[[Category:Orthopedic surgical procedures]]

Latest revision as of 20:44, 1 December 2024

Autologous chondrocyte implantation
Autologous Chondrocyte Implantation
SpecialtyOrthopedia

Autologous chondrocyte implantation (ACI, ATC code M09AX02 (WHO)) is a biomedical treatment that repairs damages in articular cartilage. ACI provides pain relief while at the same time slowing down the progression or considerably delaying partial or total joint replacement (knee replacement) surgery.

ACI procedures aim to provide complete hyaline repair tissues for articular cartilage repair. Over the last 20 years, the procedure has become more widespread and it is currently probably the most developed articular cartilage repair technique.

The procedure fails in about 15% of people.[1]

Complications

[edit]

The occurrence of subsequent surgical procedures (SSPs), primarily arthroscopy, following ACI is common. For example, in the Study of the Treatment of Articular Repair (STAR), 49% of Carticel ACI patients underwent an SSP on the treated knee, during the 4-year follow up. The most common serious adverse events (up to 5% of patients), include arthrofibrosis and joint adhesions, graft overgrowth, chondromalacia or chondrosis, cartilage injury, graft complication, meniscal lesion, graft delamination, and osteoarthritis.[2]

A recent study from Germany, published in the November 2008 issue of the American Journal of Sports Medicine, analyzed 349 ACI procedures of the knee joint. Three different ACI techniques were used. A major proportion of complications after ACI can be summarized by 4 major diagnoses: symptomatic hypertrophy, disturbed fusion, delamination, and graft failure. Among those, the overall complication rate and incidence of hypertrophy of the transplant were higher for periosteum-covered ACI. Furthermore, an increased rate of symptomatic hypertrophy was found for patellar defects.[3]

Improvement of ACI

[edit]

Techniques such as the EELS-TALC[4] to enhance ACI and its next generation advancement called Matrix Assisted Chondrocyte Implantation (MACI)[5] with enabling chondrocytes to be tissue engineered with long term native knee cartilage phenotype maintenance in vitro and in vivo,[6][7] with the engineered tissue construct containing stem cell progenitors[8] along with those expressing pluripotency markers[9] and with added advantage of enriched hyaluronic acid (HA) expression[10] by the cells have been reported which will contribute to improved regenerative therapies for cartilage damage.

References

[edit]
  1. ^ Andriolo, L; Merli, G; Filardo, G; Marcacci, M; Kon, E (March 2017). "Failure of Autologous Chondrocyte Implantation". Sports Medicine and Arthroscopy Review. 25 (1): 10–18. doi:10.1097/JSA.0000000000000137. PMID 28045868. S2CID 19085219.
  2. ^ Source: Carticel.
  3. ^ Source: Philipp Niemeyer, MD, et al.: "Characteristic Complications After Autologous Chondrocyte Implantation for Cartilage Defects of the Knee Joint". The American Journal of Sports Medicine 36:2091–2099 (2008).
  4. ^ "EELS-TALC". EELS-TALC. Retrieved 20 March 2021.
  5. ^ Jacobi, M (2011). "MACI - a new era?". Sports Med Arthrosc Rehabil Ther Technol. 3 (1): 10. doi:10.1186/1758-2555-3-10. PMC 3117745. PMID 21599919.
  6. ^ Yasuda, Ayuko (2006). "In vitro culture of chondrocytes in a novel thermoreversible gelation polymer scaffold containing growth factors". Tissue Engineering. 12 (5): 1237–1245. doi:10.1089/ten.2006.12.1237. PMID 16771637.
  7. ^ Arumugam, S (2007). "Transplantation of autologous chondrocytes ex-vivo expanded using Thermoreversible Gelation Polymer in a rabbit model of articular cartilage defect". Journal of Orthopedics. 14 (2): 223–225. doi:10.1016/j.jor.2017.01.003. PMC 5293721. PMID 28203047.
  8. ^ Katoh, Shojiro (2021). "A three-dimensional in vitro culture environment of a novel polymer scaffold, yielding chondroprogenitors and mesenchymal stem cells in human chondrocytes derived from osteoarthritis-affected cartilage tissue". Journal of Orthopedics. 23: 138–141. doi:10.1016/j.jor.2021.01.005. ISSN 0972-978X. PMC 7815488. PMID 33510554.
  9. ^ Katoh, Shojiro (2020). "Articular chondrocytes from osteoarthritic knee joints of elderly, in vitro expanded in thermo-reversible gelation polymer (TGP), exhibiting higher UEA-1 expression in lectin microarray". Regenerative Therapy. 14: 234–237. doi:10.1016/j.reth.2020.03.006. PMC 7229400. PMID 32435676.
  10. ^ Katoh, Shojiro (2021). "Enhanced expression of hyaluronic acid in osteoarthritis-affected knee-cartilage chondrocytes during three-dimensional in vitro culture in a hyaluronic-acid-retaining polymer scaffold". The Knee. 29: 365–373. doi:10.1016/j.knee.2021.02.019. PMID 33690017.