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Background. One of the most plentiful sources for MSCs is the bone marrow; however, it is unknown whether MSC yield differs among different bone marrow sites. In this study, we quantified cellular yield and evaluated resident MSC population from five bone marrow sites in the porcine model. In addition, we assessed the feasibility of a commercially...
Citations
... One of the main BMA collection sites is the posterior iliac crest, as it offers a greater number of viable cells [85]. However, the quality of the aspirate is dependent on the technique used for collection: while the first 4-5 mL of BMA contains high-quality MSCs, withdrawing larger volumes leads to the dilution of the aspirate with peripheral blood [86]. The collection of small volumes in various subcortical areas appears to be more effective, resulting in a greater yield of stem cell progenitors [87]. ...
Spinal cord injury (SCI) represents a severe trauma to the nervous system, leading to significant neurological damage, chronic inflammation, and persistent neuropathic pain. Current treatments, including pharmacotherapy, immobilization, physical therapy, and surgical interventions , often fall short in fully addressing the underlying pathophysiology and resultant disabilities. Emerging research in the field of regenerative medicine has introduced innovative approaches such as autologous orthobiologic therapies, with bone marrow aspirate (BMA) being particularly notable for its regenerative and anti-inflammatory properties. This review focuses on the potential of BMA to modulate inflammatory pathways, enhance tissue regeneration, and restore neurological function disrupted by SCI. We hypothesize that BMA's bioactive components may stimulate reparative processes at the cellular level, particularly when applied at strategic sites like the sacral hiatus to influence lumbar centers and higher neurological structures. By exploring the mechanisms through which BMA influences spinal repair, this review aims to establish a foundation for its application in clinical settings, potentially offering a transformative approach to SCI management that extends beyond symptomatic relief to promoting functional recovery.
... MSC collection from the BM isolates only approximately 0.001−0.01% of the total MSCs, which need to be expanded in vitro to a higher passage number. Consequently, the isolated cells lose their potency and genetic stability [65,88,89]. In terms of differentiation potentials, BMMSCs have better chondrogenic and osteogenic potentials than adipogenesis. ...
The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated the discovery of therapies for various illnesses. MSCs can be isolated from infant and adult tissue sources, which means they are easily available. However, this raises concerns because of the heterogeneity among the various MSC sources, which limits their effective use. Variabilities arise from donor- and tissue-specific differences, such as age, sex, and tissue source. Moreover, adult-sourced MSCs have limited proliferation potentials, which hinders their long-term therapeutic efficacy. These limitations of adult MSCs have prompted researchers to develop a new method for generating MSCs. Pluripotent stem cells (PSCs), such as embryonic stem cells and induced PSCs (iPSCs), can differentiate into various types of cells. Herein, a thorough review of the characteristics, functions, and clinical importance of MSCs is presented. The existing sources of MSCs, including adult- and infant-based sources, are compared. The most recent techniques for deriving MSCs from iPSCs, with a focus on biomaterial-assisted methods in both two- and three-dimensional culture systems, are listed and elaborated. Finally, several opportunities to develop improved methods for efficiently producing MSCs with the aim of advancing their various clinical applications are described.
Supplementary Information
The online version contains supplementary material available at 10.1186/s40824-023-00371-0.
... Recently, MSCs have been harvested from BM of long bones such as the femur (proximal and distal), tibia, humeral head, radius, ilium, etc [39,40]. The posterior part of the iliac crest is preferred for obtaining autologous stem cells as it contains the highest amount of nucleated cells (25.1-54.7) ...
Mesenchymal stromal cells (MSCs) are cells with the characteristic ability of self-renewal along with the ability to exhibit multilineage differentiation. Bone marrow (BM) is the first tissue in which MSCs were identified and BM-MSCs are most commonly used among various MSCs in clinical settings. MSCs can stimulate and promote osseous regeneration. Due to the difference in the development of long bones and craniofacial bones, the mandibular-derived MSCs (M-MSCs) have distinct differentiation characteristics as compared to that of long bones. Both mandibular and long bone-derived MSCs are positive for MSC-associated markers such as CD-73,-105, and-106, stage-specific embryonic antigen 4 and Octamer-4, and negative for hematopoietic markers such as CD-14, -34, and-45. As the M-MSCs are derived from neural crest cells, they have embryogenic cells which promote bone repair and high osteogenic potential. In vitro and in vivo animal-based studies demonstrate a higher rate of proliferation and high osteogenic potential for M-MSCs as compared to long-bones MSCs, but in vivo studies in human subjects are lacking. The BM-MSCs have their advantages and limitations. M-MSCs may be utilized as an alternative source of MSCs which can be utilized for tissue engineering and promoting the regeneration of bone. M-MSCs may have potential advantages in the repair of craniofacial or orofacial defects. Considering the utility of M-MSCs in the field of orthopaedics, we have discussed various unresolved questions, which need to be explored for their better utility in clinical practice.
... BMAC is typically isolated from the iliac crest (anterior or posterior), which is considered the "gold standard" due to its prominence and ease of collection [47]. Nevertheless, there is a recent increase of interest in an even simpler approach to retrieve BMAC by harvesting bone marrow directly from the proximal tibia instead of the iliac crest when treating knee pathologies. ...
Purpose
To compare the number and properties of bone marrow stromal cells (BMSCs) collected from bone marrow aspirate concentrate (BMAC) obtained from different harvest sites and from patients of different ages.
Methods
BMAC was obtained from two groups of patients based on age ( n = 10 per group): 19.0 ± 2.7 years for the younger and 56.8 ± 12.5 for the older group. In the latter, BMAC was obtained from both iliac crest and proximal tibia for a donor-matched analysis. Mononucleated cell count and CFU-F assay were performed, together with phenotype characterization of BMSCs from iliac crest and proximal tibia, the study of chondrogenic and osteogenic differentiation capacity, histological staining and spectrophotometric quantification, and the analysis of mRNAs expression.
Results
Cells derived from iliac crest and proximal tibia showed the same phenotypic pattern at flow cytometry, as well as similar chondrogenic and osteogenic potential. However, a significantly higher number of mononuclear cells per ml was observed in younger patients (3.8 ± 1.8 × 10 ⁷ ) compared to older patients (1.2 ± 0.8 × 10 ⁷ ) ( p < 0.0005). The latter yield, obtained from the iliac crest, was significantly higher than resulting from the BMAC harvested from the proximal tibia in the same group of patients (0.3 ± 0.2 × 10 ⁷ , p < 0.0005). This result was confirmed by the CFU-F analysis at day 10 (15.9 ± 19.4 vs 0.6 ± 1.0, p = 0.001) and day-20 (21.7 ± 23.0 vs 2.9 ± 4.2, p = 0.006).
Conclusion
Harvest site and age can affect the quality of BMAC. BMSCs obtained from iliac crest and proximal tibia present comparable mesenchymal markers expression as well as osteogenic and chondrogenic differentiation potential, but iliac crest BMAC presents a four times higher number of mononucleated cells with significantly higher clonogenic capacity compared to the tibia. BMAC of younger patients also had a three-time higher number of mononucleated cells. The identification of BMAC characteristics could help to optimize its preparation and to identify the most suitable indications for this orthobiologic treatment in the clinical practice.
... In adults, the red bone marrow is a rich source of bone marrow-derived cells and present in most skeletal system bones of the iliac crest, tibia, spine vertebrae, humerus, calcaneus, ribs, and near point of attachment of long bones of legs and arms. In this wellshielded environment, an estimate of 500 billion cells per day can be produced, in particular erythrocytes, granulocytes, and platelets [120]. For orthobiological applications, the red bone marrow is the preferred type as it contains myeloid and lymphoid stem cells and MSCs. ...
... In humans, the most common anatomical location to obtain BM is the iliac crest, but other BMA sites have been utilized [8]. Recently, McDaniel and co-workers, reported that all studied anatomical bone marrow harvesting locations contained MSCs, but the iliac crest was the most abundant source of MSCs [120], in particular posterior superior iliac spine (PSIS) [152]. ...
In recent years, autologous biological preparations have emerged as a growing area of medical innovation in interventional orthopedical procedures and surgical interventions. These cellular therapies are often referred to as orthobiologics. These preparations are derived from patient’s own tissues, including blood, bone marrow, and fat tissue to prepare platelet-rich plasma (PRP), bone marrow concentrate (BMC), and adipose tissue concentrate (ATC), respectively. Orthobiologics comprise signaling cells and molecules have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans by stimulating and enhancing tissue repair. There is a global unmet need for tissue repair strategies to treat musculoskeletal disorders (MSK), osteoarthritis (OA), and spinal maladies. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. Progress has been made in understanding orthobiological technologies and clinical applications. However, definitive and accepted standards to prepare different orthobiological bioformulation are still lacking. In this chapter, we will discuss recent developments regarding autologous orthobiological preparations and compositions regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, inflammation, angiogenesis, and pain killing effects. Readers are advised to use best clinical judgment when applying orthobiologics in musculoskeletal medicine and understand FDA regulatory limitations in use of such products when treating patients.
... A. BM-SMCs and bone marrow aspirate concentrate (BMAC) MSCs in bone marrow aspirates represent only 0.001-0.01% of mononuclear cells, even when harvested from the iliac crest, which has the highest percentage of MSCs [91,92]. BMAC is the concentration of the whole marrow aspirate in order to concentrate nucleated cells and growth factors that potentially can enhance the amount of MSCs [93]. ...
Purpose of Review
A wide array of joint-preserving surgical techniques exists in the management of acetabular chondral defects (ACDs). The purpose of this review is to summarize the clinical outcomes of the recent biologics used to treat ACDs during hip arthroscopy.
Recent Findings
Increasing evidence is available for different biological solutions used in the hip. Studies have shown promising outcomes with minimal complications when using biologics as augmentation to microfracture (MF), including different scaffolds or stem cells, or to enhance autologous chondrocyte implantation (ACI). However, data so far is scarce, and more trials and longer follow-ups are needed to better delineate the appropriate indications and benefits for each technique.
Summary
Presently, the level of evidence is low, but in general, biologics appear safe and trend toward beneficial compared to standard surgical techniques. Augmented MF is recommended for small to medium ACDs, and matrix-assisted ACI or three-dimensional ACI is recommended for medium to large defects.
... Finally, the lack of a molecular characterization of the injected BMAC does not allow to draw conclusions about the possible correlation of clinical results and quality and composition of the harvested tissue. Still, a commercial kit already studied and commonly used in the clinical practice has been used in accordance with the manufacturer instructions, and other studies by other authors have already explored the effect in concentrating bone marrow aspirate [9,25,34]. Despite these limitations, the strengths of this study are the randomized design with double blinding, together with the long follow-up, which allowed to determine some interesting conclusions on this fashionable orthobiologic approach. ...
Purpose:
The purpose of this double-blind randomized controlled trial (RCT) was to compare clinical improvement and radiographic findings up to 2 years of follow-up of a single intra-articular injection of bone marrow aspirate concentrate (BMAC) versus hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA). The hypothesis was that BMAC injection could lead to better clinical and radiographic results compared to viscosupplementation.
Methods:
Patients with bilateral knee OA were randomized to one intra-articular injection of tibial-derived BMAC in one knee and one HA injection in the contralateral knee. Sixty patients were enrolled, and 56 were studied up to the final follow-up (35 men, 21 women, mean age 57.8 ± 8.9 years), for a total of 112 knees. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the IKDC subjective score, VAS for pain, and the KOOS score. Minimal clinically important difference (MCID), patient treatment judgement, and adverse events were documented, as well as bilateral X-Rays (Rosenberg view) before and after treatment.
Results:
No severe adverse events nor differences were reported in terms of mild adverse events (7.1% vs 5.4%, p = ns) and treatment failures (10.7% vs 12.5%, p = ns) in BMAC and HA groups, respectively. The IKDC subjective score improved from baseline to all follow-ups for BMAC (p < 0.0005), while it improved up to 12 months (p < 0.0005) and then decreased at 24 months (p = 0.030) for HA. Compared to HA, BMAC showed a higher improvement for VAS pain at 12 (2.2 ± 2.6 vs 1.7 ± 2.5, p = 0.041) and 24 months (2.2 ± 2.6 vs 1.4 ± 2.8, p = 0.002). The analysis based on OA severity confirmed this difference only in Kellgren-Lawrence 1-2 knees, while comparable results were observed in moderate/severe OA. Radiographic evaluation did not show knee OA deterioration for both treatment groups, without intergroup differences.
Conclusion:
BMAC did not demonstrate a clinically significant superiority at short-term compared to viscosupplementation, reporting overall comparable results in terms of clinical scores, failures, adverse events, radiographic evaluation, MCID achievement, and patient treatment judgment. However, while HA results decreased over time, BMAC presented more durable results in mild OA knees.
Level of evidence:
Level I.
... d Quantification of AR staining intensity (after solubilization) from hip-derived (gray bar) and femur-derived (black bar) osteogenic cultures (n = 8). Data presented as mean ± SEM [44,45]. Comparisons of marrow-derived mesenchymal cells from human ilia and femurs, however, have revealed conflicting results, with some yielding similar properties [46][47][48][49][50][51], while others have observed higher concentrations of osteogenic progenitors in marrow from the iliac crest [52,53] or from the femur [54,55]. ...
Background:
Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer-irrigator-aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.
Methods:
Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft, syngeneic iliac crest allograft, and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation, and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.
Results:
Although no differences were observed between groups in CT fusion mass volumes, iliac allografts displayed an increased number of radiographically fused fusion masses and a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow.
Conclusions:
This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.
... Since a key element to the clinical success of autograft bone is the presence of osteogenic cells, we compared the colony-forming and osteogenic capacity of bone marrow cells derived from the femur and ilium. Similar to our observations, previous animal studies in dogs and pigs observed higher CFU-F frequency in bone marrow derived from the iliac crest than from the femur [47,48]. Comparisons of marrow-derived mesenchymal cells from human ilia and femurs, however, have revealed conflicting results, with some yielding similar properties [49][50][51][52][53][54], while others have observed higher concentrations of osteogenic progenitors in marrow from the iliac crest [55,56], or from the femur [57,58]. ...
Background: Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer–irrigator–aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.
Methods: Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft; syngeneic iliac crest allograft; and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.
Results: Although no differences were observed between groups in CT fusion rates or fusion mass volumes, iliac allografts displayed a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow.
Conclusions: This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.
... Since a key element to the clinical success of autograft bone is the presence of osteogenic cells, we compared the colony-forming and osteogenic capacity of bone marrow cells derived from the femur and ilium. Similar to our observations, previous animal studies in dogs and pigs observed higher CFU-F frequency in bone marrow derived from the iliac crest than from the femur [46,47]. Comparisons of marrow-derived mesenchymal cells from human ilia and femurs, however, have revealed con icting results, with some yielding similar properties [48][49][50][51][52][53], while others have observed higher concentrations of osteogenic progenitors in marrow from the iliac crest [54,55], or from the femur [56,57]. ...
Background: Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer–irrigator–aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.
Methods: Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft; syngeneic iliac crest allograft; and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.
Results: Although no differences were observed between groups in CT fusion mass volumes, iliac allografts displayed an increased number of radiographically fused fusion masses and a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow.
Conclusions: This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.
