Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®)

Preclinical and clinical trial in osteoarthritis of the knee joint

Pawan Kumar Gupta, Anoop Chullikana, Mathiyazhagan Rengasamy, Naresh Shetty, Vivek Pandey, Vikas Agarwal, Shrikant Yeshwant Wagh, Prasanth Kulapurathu Vellotare, Devi Damodaran, Pachaiyappan Viswanathan, Charan Thej, Sudha Balasubramanian, Anish Sen Majumdar

Research output: Contribution to journalArticle

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Abstract

Background: Osteoarthritis (OA) is a common and debilitating chronic degenerative disease of the joints. Currently, cell-based therapy is being explored to address the repair of damaged articular cartilage in the knee joint. Methods: The in vitro differentiation potential of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®) was determined by differentiating the cells toward the chondrogenic lineage and quantifying sulfated glycosaminoglycan (sGAG). The mono-iodoacetate (MIA)-induced preclinical model of OA has been used to demonstrate pain reduction and cartilage formation. In the clinical study, 60 OA patients were randomized to receive different doses of cells (25, 50, 75, or 150 million cells) or placebo. Stempeucel® was administered by intra-articular (IA) injection into the knee joint, followed by 2ml hyaluronic acid (20mg). Subjective evaluations-visual analog scale (VAS) for pain, intermittent and constant osteoarthritis pain (ICOAP), and Western Ontario and McMaster Universities Osteoarthritis (WOMAC-OA) index-were performed at baseline and at 1, 3, 6, and 12months of follow-up. Magnetic resonance imaging of the knee was performed at baseline, and at 6 and 12months follow-up for cartilage evaluation. Results: Stempeucel® differentiated into the chondrogenic lineage in vitro with downregulation of Sox9 and upregulation of Col2A genes. Furthermore, Stempeucel® differentiated into chondrocytes and synthesized a significant amount of sGAG (30±1.8μg/μg GAG/DNA). In the preclinical model of OA, Stempeucel® reduced pain significantly and also repaired damaged articular cartilage in rats. In the clinical study, IA administration of Stempeucel® was safe, and a trend towards improvement was seen in the 25-million-cell dose group in all subjective parameters (VAS, ICOAP, andWOMAC-OA scores), although this was not statistically significant when compared to placebo. Adverse events were predominant in the higher dose groups (50, 75, and 150 million cells). Knee pain and swelling were the most common adverse events. The whole-organ magnetic resonance imaging score of the knee did not reveal any difference from baseline and the placebo group. Conclusion: Intra-articular administration of Stempeucel® is safe. A twenty-five-million-cell dose may be the most effective among the doses tested for pain reduction. Clinical studies with a larger patient population are required to demonstrate a robust therapeutic efficacy of Stempeucel® in OA. Trial registration: Clinicaltrials.gov NCT01453738. Registered 13 October 2011.

Original languageEnglish
Article number301
JournalArthritis Research and Therapy
Volume18
Issue number1
DOIs
Publication statusPublished - 20-12-2016

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Knee Osteoarthritis
Knee Joint
Mesenchymal Stromal Cells
Osteoarthritis
Bone Marrow
Clinical Trials
Safety
A73025
Pain
Knee
Joints
Placebos
Articular Cartilage
Cartilage
Magnetic Resonance Imaging
Iodoacetates
Intra-Articular Injections
Ontario
Pain Measurement
Hyaluronic Acid

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Gupta, Pawan Kumar ; Chullikana, Anoop ; Rengasamy, Mathiyazhagan ; Shetty, Naresh ; Pandey, Vivek ; Agarwal, Vikas ; Wagh, Shrikant Yeshwant ; Vellotare, Prasanth Kulapurathu ; Damodaran, Devi ; Viswanathan, Pachaiyappan ; Thej, Charan ; Balasubramanian, Sudha ; Majumdar, Anish Sen. / Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®) : Preclinical and clinical trial in osteoarthritis of the knee joint. In: Arthritis Research and Therapy. 2016 ; Vol. 18, No. 1.
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title = "Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel{\circledR}): Preclinical and clinical trial in osteoarthritis of the knee joint",
abstract = "Background: Osteoarthritis (OA) is a common and debilitating chronic degenerative disease of the joints. Currently, cell-based therapy is being explored to address the repair of damaged articular cartilage in the knee joint. Methods: The in vitro differentiation potential of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel{\circledR}) was determined by differentiating the cells toward the chondrogenic lineage and quantifying sulfated glycosaminoglycan (sGAG). The mono-iodoacetate (MIA)-induced preclinical model of OA has been used to demonstrate pain reduction and cartilage formation. In the clinical study, 60 OA patients were randomized to receive different doses of cells (25, 50, 75, or 150 million cells) or placebo. Stempeucel{\circledR} was administered by intra-articular (IA) injection into the knee joint, followed by 2ml hyaluronic acid (20mg). Subjective evaluations-visual analog scale (VAS) for pain, intermittent and constant osteoarthritis pain (ICOAP), and Western Ontario and McMaster Universities Osteoarthritis (WOMAC-OA) index-were performed at baseline and at 1, 3, 6, and 12months of follow-up. Magnetic resonance imaging of the knee was performed at baseline, and at 6 and 12months follow-up for cartilage evaluation. Results: Stempeucel{\circledR} differentiated into the chondrogenic lineage in vitro with downregulation of Sox9 and upregulation of Col2A genes. Furthermore, Stempeucel{\circledR} differentiated into chondrocytes and synthesized a significant amount of sGAG (30±1.8μg/μg GAG/DNA). In the preclinical model of OA, Stempeucel{\circledR} reduced pain significantly and also repaired damaged articular cartilage in rats. In the clinical study, IA administration of Stempeucel{\circledR} was safe, and a trend towards improvement was seen in the 25-million-cell dose group in all subjective parameters (VAS, ICOAP, andWOMAC-OA scores), although this was not statistically significant when compared to placebo. Adverse events were predominant in the higher dose groups (50, 75, and 150 million cells). Knee pain and swelling were the most common adverse events. The whole-organ magnetic resonance imaging score of the knee did not reveal any difference from baseline and the placebo group. Conclusion: Intra-articular administration of Stempeucel{\circledR} is safe. A twenty-five-million-cell dose may be the most effective among the doses tested for pain reduction. Clinical studies with a larger patient population are required to demonstrate a robust therapeutic efficacy of Stempeucel{\circledR} in OA. Trial registration: Clinicaltrials.gov NCT01453738. Registered 13 October 2011.",
author = "Gupta, {Pawan Kumar} and Anoop Chullikana and Mathiyazhagan Rengasamy and Naresh Shetty and Vivek Pandey and Vikas Agarwal and Wagh, {Shrikant Yeshwant} and Vellotare, {Prasanth Kulapurathu} and Devi Damodaran and Pachaiyappan Viswanathan and Charan Thej and Sudha Balasubramanian and Majumdar, {Anish Sen}",
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Gupta, PK, Chullikana, A, Rengasamy, M, Shetty, N, Pandey, V, Agarwal, V, Wagh, SY, Vellotare, PK, Damodaran, D, Viswanathan, P, Thej, C, Balasubramanian, S & Majumdar, AS 2016, 'Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®): Preclinical and clinical trial in osteoarthritis of the knee joint', Arthritis Research and Therapy, vol. 18, no. 1, 301. https://doi.org/10.1186/s13075-016-1195-7

Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®) : Preclinical and clinical trial in osteoarthritis of the knee joint. / Gupta, Pawan Kumar; Chullikana, Anoop; Rengasamy, Mathiyazhagan; Shetty, Naresh; Pandey, Vivek; Agarwal, Vikas; Wagh, Shrikant Yeshwant; Vellotare, Prasanth Kulapurathu; Damodaran, Devi; Viswanathan, Pachaiyappan; Thej, Charan; Balasubramanian, Sudha; Majumdar, Anish Sen.

In: Arthritis Research and Therapy, Vol. 18, No. 1, 301, 20.12.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®)

T2 - Preclinical and clinical trial in osteoarthritis of the knee joint

AU - Gupta, Pawan Kumar

AU - Chullikana, Anoop

AU - Rengasamy, Mathiyazhagan

AU - Shetty, Naresh

AU - Pandey, Vivek

AU - Agarwal, Vikas

AU - Wagh, Shrikant Yeshwant

AU - Vellotare, Prasanth Kulapurathu

AU - Damodaran, Devi

AU - Viswanathan, Pachaiyappan

AU - Thej, Charan

AU - Balasubramanian, Sudha

AU - Majumdar, Anish Sen

PY - 2016/12/20

Y1 - 2016/12/20

N2 - Background: Osteoarthritis (OA) is a common and debilitating chronic degenerative disease of the joints. Currently, cell-based therapy is being explored to address the repair of damaged articular cartilage in the knee joint. Methods: The in vitro differentiation potential of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®) was determined by differentiating the cells toward the chondrogenic lineage and quantifying sulfated glycosaminoglycan (sGAG). The mono-iodoacetate (MIA)-induced preclinical model of OA has been used to demonstrate pain reduction and cartilage formation. In the clinical study, 60 OA patients were randomized to receive different doses of cells (25, 50, 75, or 150 million cells) or placebo. Stempeucel® was administered by intra-articular (IA) injection into the knee joint, followed by 2ml hyaluronic acid (20mg). Subjective evaluations-visual analog scale (VAS) for pain, intermittent and constant osteoarthritis pain (ICOAP), and Western Ontario and McMaster Universities Osteoarthritis (WOMAC-OA) index-were performed at baseline and at 1, 3, 6, and 12months of follow-up. Magnetic resonance imaging of the knee was performed at baseline, and at 6 and 12months follow-up for cartilage evaluation. Results: Stempeucel® differentiated into the chondrogenic lineage in vitro with downregulation of Sox9 and upregulation of Col2A genes. Furthermore, Stempeucel® differentiated into chondrocytes and synthesized a significant amount of sGAG (30±1.8μg/μg GAG/DNA). In the preclinical model of OA, Stempeucel® reduced pain significantly and also repaired damaged articular cartilage in rats. In the clinical study, IA administration of Stempeucel® was safe, and a trend towards improvement was seen in the 25-million-cell dose group in all subjective parameters (VAS, ICOAP, andWOMAC-OA scores), although this was not statistically significant when compared to placebo. Adverse events were predominant in the higher dose groups (50, 75, and 150 million cells). Knee pain and swelling were the most common adverse events. The whole-organ magnetic resonance imaging score of the knee did not reveal any difference from baseline and the placebo group. Conclusion: Intra-articular administration of Stempeucel® is safe. A twenty-five-million-cell dose may be the most effective among the doses tested for pain reduction. Clinical studies with a larger patient population are required to demonstrate a robust therapeutic efficacy of Stempeucel® in OA. Trial registration: Clinicaltrials.gov NCT01453738. Registered 13 October 2011.

AB - Background: Osteoarthritis (OA) is a common and debilitating chronic degenerative disease of the joints. Currently, cell-based therapy is being explored to address the repair of damaged articular cartilage in the knee joint. Methods: The in vitro differentiation potential of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®) was determined by differentiating the cells toward the chondrogenic lineage and quantifying sulfated glycosaminoglycan (sGAG). The mono-iodoacetate (MIA)-induced preclinical model of OA has been used to demonstrate pain reduction and cartilage formation. In the clinical study, 60 OA patients were randomized to receive different doses of cells (25, 50, 75, or 150 million cells) or placebo. Stempeucel® was administered by intra-articular (IA) injection into the knee joint, followed by 2ml hyaluronic acid (20mg). Subjective evaluations-visual analog scale (VAS) for pain, intermittent and constant osteoarthritis pain (ICOAP), and Western Ontario and McMaster Universities Osteoarthritis (WOMAC-OA) index-were performed at baseline and at 1, 3, 6, and 12months of follow-up. Magnetic resonance imaging of the knee was performed at baseline, and at 6 and 12months follow-up for cartilage evaluation. Results: Stempeucel® differentiated into the chondrogenic lineage in vitro with downregulation of Sox9 and upregulation of Col2A genes. Furthermore, Stempeucel® differentiated into chondrocytes and synthesized a significant amount of sGAG (30±1.8μg/μg GAG/DNA). In the preclinical model of OA, Stempeucel® reduced pain significantly and also repaired damaged articular cartilage in rats. In the clinical study, IA administration of Stempeucel® was safe, and a trend towards improvement was seen in the 25-million-cell dose group in all subjective parameters (VAS, ICOAP, andWOMAC-OA scores), although this was not statistically significant when compared to placebo. Adverse events were predominant in the higher dose groups (50, 75, and 150 million cells). Knee pain and swelling were the most common adverse events. The whole-organ magnetic resonance imaging score of the knee did not reveal any difference from baseline and the placebo group. Conclusion: Intra-articular administration of Stempeucel® is safe. A twenty-five-million-cell dose may be the most effective among the doses tested for pain reduction. Clinical studies with a larger patient population are required to demonstrate a robust therapeutic efficacy of Stempeucel® in OA. Trial registration: Clinicaltrials.gov NCT01453738. Registered 13 October 2011.

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